CoChat
Sign Up
Cited by 549MicroRNA in disease regulationCancer-related molecular mechanisms researchCancer-related Molecular Pathways

The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics

Open access
Bautista-Sánchez, Diana, Arriaga-Canon, Cristian, Pedroza-Torres, Abraham, De La Rosa-Velázquez, Inti Alberto, González-Barrios, Rodrigo, Contreras-Espinosa, Laura, Montiel-Manríquez, Rogelio, Castro-Hernández, Clementina +3 more·2020·Molecular Therapy Nucleic Acids
DOI 10.1016/j.omtn.2020.03.003PMC PMC7118281
Open this paper in CoChat — free accountOpen PDF

Abstract

MicroRNAs are small noncoding transcripts that posttranscriptionally regulate gene expression via base-pairing complementarity. Their role in cancer can be related to tumor suppression or oncogenic function. Moreover, they have been linked to processes recognized as hallmarks of cancer, such as apoptosis, invasion, metastasis, and proliferation. Particularly, one of the first oncomiRs found upregulated in a variety of cancers, such as gliomas, breast cancer, and colorectal cancer, was microRNA-21 (miR-21). Some of its target genes associated with cancer are PTEN (phosphatase and tensin homolog), PDCD4 (programmed cell death protein 4), RECK (reversion-inducing cysteine-rich protein with Kazal motifs), and STAT3 (signal transducer activator of transcription 3). As a result, miR-21 has been proposed as a plausible diagnostic and prognostic biomarker, as well as a therapeutic target for several types of cancer. Currently, research and clinical trials to inhibit miR-21 through anti-miR-21 oligonucleotides and ADM-21 are being conducted. As all of the evidence suggests, miR-21 is involved in carcinogenic processes; therefore, inhibiting it could have effects on more than one type of cancer. However, whether miR-21 can be used as a tissue-specific biomarker should be analyzed with caution. Consequently, the purpose of this review is to outline the available information and recent advances regarding miR-21 as a potential biomarker in the clinical setting and as a therapeutic target in cancer to highlight its importance in the era of precision medicine.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.omtn.2020.03.003

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • miR-21 has been reported to be associated with GBM aggressiveness in previous studies.

    “We explored miR-21 as a potential biomarker due to its reported association with GBM aggressiveness in previous studies by various research groups [8,23,24].”

    From miR-21 as a diagnostic and prognostic biomarker in glioma: tissue and serum expression analysis in a Pakistani cohort (2026) · cites this paper as [24]

    The miR-21 Pathways section links miR-21 to cancer-related proliferation and identifies SPRY2 as a target; the References list a study reporting that miR-21 triggers malignancy in human gliomas. These passages support an association with glioma aggressiveness, but they do not specifically establish it for glioblastoma (GBM). Page numbers were not available in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 148

  1. [2]Ambros V. Bartel B. Bartel D.P. Burge C.B. Carrington J.C. Chen X. Dreyfuss G. Eddy S.R. Griffiths-Jones S. Marshall M. A uniform system for microRNA annotation RNA 9 2003 277 279 12592000 PMC1370393
  2. [3]Bartel D.P. MicroRNAs: target recognition and regulatory functions Cell 136 2009 215 233 19167326 PMC3794896
  3. [4]Doench J.G. Sharp P.A. Specificity of microRNA target selection in translational repression Genes Dev. 18 2004 504 511 15014042 PMC374233
  4. [5]Seitz H. Issues in current microRNA target identification methods RNA Biol. 14 2017 831 834 28430005 PMC5546714
  5. [6]Ivey K.N. Srivastava D. MicroRNAs as developmental regulators Cold Spring Harb. Perspect. Biol. 7 2015 a008144 26134312 PMC4484971
  6. [7]Sayed D. Abdellatif M. MicroRNAs in development and disease Physiol. Rev. 91 2011 827 887 21742789
  7. [8]Croce C.M. Calin G.A. miRNAs, cancer, and stem cell division Cell 122 2005 6 7 16009126
  8. [9]Bueno M.J. Malumbres M. MicroRNAs and the cell cycle Biochim. Biophys. Acta 1812 2011 592 601 21315819
  9. [10]Hydbring P. Wang Y. Fassl A. Li X. Matia V. Otto T. Choi Y.J. Sweeney K.E. Suski J.M. Yin H. Cell-cycle-targeting microRNAs as therapeutic tools against refractory cancers Cancer Cell 31 2017 576 590.e8 28399412 PMC5425285
  10. [11]Jovanovic M. Hengartner M.O. miRNAs and apoptosis: RNAs to die for Oncogene 25 2006 6176 6187 17028597
  11. [12]Su Z. Yang Z. Xu Y. Chen Y. Yu Q. MicroRNAs in apoptosis, autophagy and necroptosis Oncotarget 6 2015 8474 8490 25893379 PMC4496162
  12. [13]Vienberg S. Geiger J. Madsen S. Dalgaard L.T. MicroRNAs in metabolism Acta Physiol. (Oxf.) 219 2017 346 361 27009502 PMC5297868
  13. [14]Rottiers V. Näär A.M. MicroRNAs in metabolism and metabolic disorders Nat. Rev. Mol. Cell Biol. 13 2012 239 250 22436747 PMC4021399
  14. [15]Yao S. MicroRNA biogenesis and their functions in regulating stem cell potency and differentiation Biol. Proced. Online 18 2016 8 26966421 PMC4785656
  15. [16]Lou W. Liu J. Gao Y. Zhong G. Chen D. Shen J. Bao C. Xu L. Pan J. Cheng J. MicroRNAs in cancer metastasis and angiogenesis Oncotarget 8 2017 115787 115802 29383201 PMC5777813
  16. [17]Ma L. MicroRNA and metastasis Adv. Cancer Res. 132 2016 165 207 27613133
  17. [18]Li S. Liang Z. Xu L. Zou F. MicroRNA-21: a ubiquitously expressed pro-survival factor in cancer and other diseases Mol. Cell. Biochem. 360 2012 147 158 21909994
  18. [19]Bushati N. Cohen S.M. MicroRNA functions Annu. Rev. Cell Dev. Biol. 23 2007 175 205 17506695
  19. [20]Mihailovich M. Bremang M. Spadotto V. Musiani D. Vitale E. Varano G. Zambelli F. Mancuso F.M. Cairns D.A. Pavesi G. miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth Nat. Commun. 6 2015 8725 26555894 PMC4667639
  20. [21]Vian L. Di Carlo M. Pelosi E. Fazi F. Santoro S. Cerio A.M. Boe A. Rotilio V. Billi M. Racanicchi S. Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors Cell Death Differ. 21 2014 290 301 24141720 PMC3890951
  21. [22]Brenner J.L. Jasiewicz K.L. Fahley A.F. Kemp B.J. Abbott A.L. Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans Curr. Biol. 20 2010 1321 1325 20579881 PMC2946380
  22. [23]Alvarez-Saavedra E. Horvitz H.R. Many families of C. elegans microRNAs are not essential for development or viability Curr. Biol. 20 2010 367 373 20096582 PMC2844791
  23. [24]Li X. Cassidy J.J. Reinke C.A. Fischboeck S. Carthew R.W. A microRNA imparts robustness against environmental fluctuation during development Cell 137 2009 273 282 19379693 PMC2674871
  24. [25]Bartel D.P. Chen C.-Z. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs Nat. Rev. Genet. 5 2004 396 400 15143321
  25. [26]Lee Y. Kim M. Han J. Yeom K.-H. Lee S. Baek S.H. Kim V.N. MicroRNA genes are transcribed by RNA polymerase II EMBO J. 23 2004 4051 4060 15372072 PMC524334
  26. [27]Wang G. Wang Y. Shen C. Huang Y.W. Huang K. Huang T.H.M. Nephew K.P. Li L. Liu Y. RNA polymerase II binding patterns reveal genomic regions involved in microRNA gene regulation PLoS ONE 5 2010 e13798 21072189 PMC2970572
  27. [28]Cai X. Hagedorn C.H. Cullen B.R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs RNA 10 2004 1957 1966 15525708 PMC1370684
  28. [29]Borchert G.M. Lanier W. Davidson B.L. RNA polymerase III transcribes human microRNAs Nat. Struct. Mol. Biol. 13 2006 1097 1101 17099701
  29. [30]Canella D. Praz V. Reina J.H. Cousin P. Hernandez N. Defining the RNA polymerase III transcriptome: genome-wide localization of the RNA polymerase III transcription machinery in human cells Genome Res. 20 2010 710 721 20413673 PMC2877568
  30. [31]Faller M. Guo F. MicroRNA biogenesis: there’s more than one way to skin a cat Biochim. Biophys. Acta 1779 2008 663 667 18778799 PMC2633599
  31. [32]Denli A.M. Tops B.B.J. Plasterk R.H.A. Ketting R.F. Hannon G.J. Processing of primary microRNAs by the Microprocessor complex Nature 432 2004 231 235 15531879
  32. [33]Gregory R.I. Yan K.-P. Amuthan G. Chendrimada T. Doratotaj B. Cooch N. Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs Nature 432 2004 235 240 15531877
  33. [34]Triboulet R. Chang H.-M. Lapierre R.J. Gregory R.I. Post-transcriptional control of DGCR8 expression by the Microprocessor RNA 15 2009 1005 1011 19383765 PMC2685516
  34. [35]Yi R. Qin Y. Macara I.G. Cullen B.R. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs Genes Dev. 17 2003 3011 3016 14681208 PMC305252
  35. [36]Chendrimada T.P. Gregory R.I. Kumaraswamy E. Norman J. Cooch N. Nishikura K. Shiekhattar R. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing Nature 436 2005 740 744 15973356 PMC2944926
  36. [37]Wilson R.C. Tambe A. Kidwell M.A. Noland C.L. Schneider C.P. Doudna J.A. Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis Mol. Cell 57 2015 397 407 25557550 PMC4320653
  37. [38]Koscianska E. Starega-Roslan J. Krzyzosiak W.J. The role of Dicer protein partners in the processing of microRNA precursors PLoS ONE 6 2011 e28548 22163034 PMC3232248
  38. [39]Schwarz D.S. Hutvágner G. Du T. Xu Z. Aronin N. Zamore P.D. Asymmetry in the assembly of the RNAi enzyme complex Cell 115 2003 199 208 14567917
  39. [40]Klein M. Chandradoss S.D. Depken M. Joo C. Why Argonaute is needed to make microRNA target search fast and reliable Semin. Cell Dev. Biol. 65 2017 20 28 27235676
  40. [41]Thermann R. Hentze M.W. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation Nature 447 2007 875 878 17507927
  41. [42]Morozova N. Zinovyev A. Nonne N. Pritchard L.-L. Gorban A.N. Harel-Bellan A. Kinetic signatures of microRNA modes of action RNA 18 2012 1635 1655 22850425 PMC3425779
  42. [43]Chendrimada T.P. Finn K.J. Ji X. Baillat D. Gregory R.I. Liebhaber S.A. Pasquinelli A.E. Shiekhattar R. MicroRNA silencing through RISC recruitment of eIF6 Nature 447 2007 823 828 17507929
  43. [44]Mathonnet G. Fabian M.R. Svitkin Y.V. Parsyan A. Huck L. Murata T. Biffo S. Merrick W.C. Darzynkiewicz E. Pillai R.S. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F Science 317 2007 1764 1767 17656684
  44. [45]Pillai R.S. Bhattacharyya S.N. Artus C.G. Zoller T. Cougot N. Basyuk E. Bertrand E. Filipowicz W. Inhibition of translational initiation by Let-7 microRNA in human cells Science 309 2005 1573 1576 16081698
  45. [47]Petersen C.P. Bordeleau M.-E. Pelletier J. Sharp P.A. Short RNAs repress translation after initiation in mammalian cells Mol. Cell 21 2006 533 542 16483934
  46. [48]Chang J.H. Xiang S. Xiang K. Manley J.L. Tong L. Structural and biochemical studies of the 5′→3′ exoribonuclease Xrn1 Nat. Struct. Mol. Biol. 18 2011 270 276 21297639 PMC3075561
  47. [49]Jones C.I. Zabolotskaya M.V. Newbury S.F. The 5′ → 3′ exoribonuclease XRN1/Pacman and its functions in cellular processes and development Wiley Interdiscip. Rev. RNA 3 2012 455 468 22383165
  48. [50]Jinek M. Coyle S.M. Doudna J.A. Coupled 5′ nucleotide recognition and processivity in Xrn1-mediated mRNA decay Mol. Cell 41 2011 600 608 21362555 PMC3090138
  49. [51]Chivukula R.R. Mendell J.T. Circular reasoning: microRNAs and cell-cycle control Trends Biochem. Sci. 33 2008 474 481 18774719 PMC2824243
  50. [52]Calin G.A. Sevignani C. Dumitru C.D. Hyslop T. Noch E. Yendamuri S. Shimizu M. Rattan S. Bullrich F. Negrini M. Croce C.M. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers Proc. Natl. Acad. Sci. USA 101 2004 2999 3004 14973191 PMC365734
  51. [53]Calin G.A. Dumitru C.D. Shimizu M. Bichi R. Zupo S. Noch E. Aldler H. Rattan S. Keating M. Rai K. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia Proc. Natl. Acad. Sci. USA 99 2002 15524 15529 12434020 PMC137750
  52. [54]Calin G.A. Ferracin M. Cimmino A. Di Leva G. Shimizu M. Wojcik S.E. Iorio M.V. Visone R. Sever N.I. Fabbri M. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia N. Engl. J. Med. 353 2005 1793 1801 16251535
  53. [55]Caldas C. Brenton J.D. Sizing up miRNAs as cancer genes Nat. Med. 11 2005 712 714 16015356
  54. [56]Iorio M.V. Ferracin M. Liu C.-G. Veronese A. Spizzo R. Sabbioni S. Magri E. Pedriali M. Fabbri M. Campiglio M. MicroRNA gene expression deregulation in human breast cancer Cancer Res. 65 2005 7065 7070 16103053
  55. [57]Rosenfeld N. Aharonov R. Meiri E. Rosenwald S. Spector Y. Zepeniuk M. Benjamin H. Shabes N. Tabak S. Levy A. MicroRNAs accurately identify cancer tissue origin Nat. Biotechnol. 26 2008 462 469 18362881
  56. [58]Lu J. Getz G. Miska E.A. Alvarez-Saavedra E. Lamb J. Peck D. Sweet-Cordero A. Ebert B.L. Mak R.H. Ferrando A.A. MicroRNA expression profiles classify human cancers Nature 435 2005 834 838 15944708
  57. [59]Zhang B. Pan X. Cobb G.P. Anderson T.A. MicroRNAs as oncogenes and tumor suppressors Dev. Biol. 302 2007 1 12 16989803
  58. [60]Garofalo M. Quintavalle C. Romano G. Croce C.M. Condorelli G. miR221/222 in cancer: their role in tumor progression and response to therapy Curr. Mol. Med. 12 2012 27 33 22082479 PMC3673714
  59. [61]Guttilla I.K. White B.A. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells J. Biol. Chem. 284 2009 23204 23216 19574223 PMC2749094
  60. [62]Tang W. Zhu J. Su S. Wu W. Liu Q. Su F. Yu F. miR-27 as a prognostic marker for breast cancer progression and patient survival PLoS ONE 7 2012 e51702 23240057 PMC3519894
  61. [63]Meng F. Henson R. Wehbe-Janek H. Ghoshal K. Jacob S.T. Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer Gastroenterology 133 2007 647 658 17681183 PMC4285346
  62. [64]Hu J. Ni S. Cao Y. Zhang T. Wu T. Yin X. Lang Y. Lu H. The Angiogenic effect of microRNA-21 Targeting TIMP3 through the regulation of MMP2 and MMP9 PLoS ONE 11 2016 e0149537 26872030 PMC4752282
  63. [65]Valeri N. Gasparini P. Braconi C. Paone A. Lovat F. Fabbri M. Sumani K.M. Alder H. Amadori D. Patel T. MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2) Proc. Natl. Acad. Sci. USA 107 2010 21098 21103 21078976 PMC3000294
  64. [66]Fuse M. Nohata N. Kojima S. Sakamoto S. Chiyomaru T. Kawakami K. Enokida H. Nakagawa M. Naya Y. Ichikawa T. Seki N. Restoration of miR-145 expression suppresses cell proliferation, migration and invasion in prostate cancer by targeting FSCN1 Int. J. Oncol. 38 2011 1093 1101 21258769
  65. [67]Mizuno R. Kawada K. Sakai Y. The molecular basis and therapeutic potential of Let-7 microRNAs against colorectal cancer Can. J. Gastroenterol. Hepatol 2018 2018 5769591 30018946 PMC6029494
  66. [68]Gulei D. Magdo L. Jurj A. Raduly L. Cojocneanu-Petric R. Moldovan A. Moldovan C. Florea A. Pasca S. Pop L.-A. The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal transition in colon cancer cells by indirectly up-regulating E-cadherin expression Cell Death Dis. 9 2018 66 29352232 PMC5833765
  67. [69]De Cola A. Volpe S. Budani M.C. Ferracin M. Lattanzio R. Turdo A. D’Agostino D. Capone E. Stassi G. Todaro M. miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance Cell Death Dis. 6 2015 e1823 26181203 PMC4650737
  68. [70]Lagos-Quintana M. Rauhut R. Lendeckel W. Tuschl T. Identification of novel genes coding for small expressed RNAs Science 294 2001 853 858 11679670
  69. [71]Ribas J. Ni X. Castanares M. Liu M.M. Esopi D. Yegnasubramanian S. Rodriguez R. Mendell J.T. Lupold S.E. A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts Nucleic Acids Res. 40 2012 6821 6833 22505577 PMC3413119
  70. [72]Ozsolak F. Poling L.L. Wang Z. Liu H. Liu X.S. Roeder R.G. Zhang X. Song J.S. Fisher D.E. Chromatin structure analyses identify miRNA promoters Genes Dev. 22 2008 3172 3183 19056895 PMC2593607
  71. [73]Fujita S. Ito T. Mizutani T. Minoguchi S. Yamamichi N. Sakurai K. Iba H. miR-21 gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism J. Mol. Biol. 378 2008 492 504 18384814
  72. [74]Mudduluru G. George-William J.N. Muppala S. Asangani I.A. Kumarswamy R. Nelson L.D. Allgayer H. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer Biosci. Rep. 31 2011 185 197 20815812
  73. [75]Griffiths-Jones S. Grocock R.J. van Dongen S. Bateman A. Enright A.J. miRBase: microRNA sequences, targets and gene nomenclature Nucleic Acids Res. 34 2006 D140 D144 16381832 PMC1347474
  74. [77]Kumarswamy R. Volkmann I. Thum T. Regulation and function of miRNA-21 in health and disease RNA Biol. 8 2011 706 713 21712654 PMC3256347
  75. [78]Wickramasinghe N.S. Manavalan T.T. Dougherty S.M. Riggs K.A. Li Y. Klinge C.M. Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells Nucleic Acids Res. 37 2009 2584 2595 19264808 PMC2677875
  76. [79]Zhao Q. Chen S. Zhu Z. Yu L. Ren Y. Jiang M. Weng J. Li B. miR-21 promotes EGF-induced pancreatic cancer cell proliferation by targeting Spry2 Cell Death Dis. 9 2018 1157 30464258 PMC6249286
  77. [80]Yang Y. Meng H. Peng Q. Yang X. Gan R. Zhao L. Chen Z. Lu J. Meng Q.H. Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4 Cancer Gene Ther. 22 2015 23 29 25477028
  78. [81]Xu L.F. Wu Z.P. Chen Y. Zhu Q.S. Hamidi S. Navab R. MicroRNA-21 (miR-21) regulates cellular proliferation, invasion, migration, and apoptosis by targeting PTEN, RECK and Bcl-2 in lung squamous carcinoma, Gejiu City, China PLoS ONE 9 2014 e103698 25084400 PMC4118890
  79. [82]Wu Y. Song Y. Xiong Y. Wang X. Xu K. Han B. Bai Y. Li L. Zhang Y. Zhou L. MicroRNA-21 (Mir-21) promotes cell growth and invasion by repressing tumor suppressor PTEN in colorectal cancer Cell. Physiol. Biochem. 43 2017 945 958 28957811
  80. [83]Liu Z.-L. Wang H. Liu J. Wang Z.-X. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN Mol. Cell. Biochem. 372 2013 35 45 22956424
  81. [84]Asangani I.A. Rasheed S.A. Nikolova D.A. Leupold J.H. Colburn N.H. Post S. Allgayer H. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer Oncogene 27 2008 2128 2136 17968323
  82. [85]Martin del Campo S.E. Latchana N. Levine K.M. Grignol V.P. Fairchild E.T. Jaime-Ramirez A.C. Dao T.-V. Karpa V.I. Carson M. Ganju A. miR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of miR-21 inhibitor PLoS ONE 10 2015 e0115919 25587717 PMC4294659
  83. [86]Song B. Wang C. Liu J. Wang X. Lv L. Wei L. Xie L. Zheng Y. Song X. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression J. Exp. Clin. Cancer Res. 29 2010 29 20346171 PMC2853500
  84. [87]Zhu S. Si M.-L. Wu H. Mo Y.-Y. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1) J. Biol. Chem. 282 2007 14328 14336 17363372
  85. [88]Qiu F. Tong H. Wang Y. Tao J. Wang H. Chen L. Inhibition of miR-21-5p suppresses high glucose-induced proliferation and angiogenesis of human retinal microvascular endothelial cells by the regulation of AKT and ERK pathways via maspin Biosci. Biotechnol. Biochem. 82 2018 1366 1376 29658404
  86. [91]Mei M. Ren Y. Zhou X. Yuan X.B. Han L. Wang G.X. Jia Z. Pu P.Y. Kang C.S. Yao Z. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells Technol. Cancer Res. Treat. 9 2010 77 86 20082533
  87. [92]Peng Q. Zhang X. Min M. Zou L. Shen P. Zhu Y. The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis Oncotarget 8 2017 44893 44909 28415652 PMC5546529
  88. [93]Qu K. Lin T. Pang Q. Liu T. Wang Z. Tai M. Meng F. Zhang J. Wan Y. Mao P. Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations Oncotarget 7 2016 33994 34010 27166186 PMC5085133
  89. [94]Sazanov A.A. Kiselyova E.V. Zakharenko A.A. Romanov M.N. Zaraysky M.I. Plasma and saliva miR-21 expression in colorectal cancer patients J. Appl. Genet. 58 2017 231 237 27910062
  90. [95]Zhao W. Zhao J.-J. Zhang L. Xu Q.-F. Zhao Y.-M. Shi X.-Y. Xu A.-G. Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer Int. J. Clin. Exp. Med. 8 2015 14759 14763 26628958 PMC4658847
  91. [96]Weber J.A. Baxter D.H. Zhang S. Huang D.Y. Huang K.H. Lee M.J. Galas D.J. Wang K. The microRNA spectrum in 12 body fluids Clin. Chem. 56 2010 1733 1741 20847327 PMC4846276
  92. [97]Xue X. Liu Y. Wang Y. Meng M. Wang K. Zang X. Zhao S. Sun X. Cui L. Pan L. Liu S. miR-21 and miR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN Oncotarget 7 2016 84508 84519 27811366 PMC5356677
  93. [98]Markou A. Zavridou M. Lianidou E.S. miRNA-21 as a novel therapeutic target in lung cancer Lung Cancer (Auckl.) 7 2016 19 27 28210157 PMC5310696
  94. [99]Corcoran C. Friel A.M. Duffy M.J. Crown J. O’Driscoll L. Intracellular and extracellular microRNAs in breast cancer Clin. Chem. 57 2011 18 32 21059829
  95. [100]Lehmann U. Streichert T. Otto B. Albat C. Hasemeier B. Christgen H. Schipper E. Hille U. Kreipe H.H. Länger F. Identification of differentially expressed microRNAs in human male breast cancer BMC Cancer 10 2010 109 20331864 PMC2850898
  96. [101]Gao Y. Cai Q. Huang Y. Li S. Yang H. Sun L. Chen K. Wang Y. MicroRNA-21 as a potential diagnostic biomarker for breast cancer patients: a pooled analysis of individual studies Oncotarget 7 2016 34498 34506 27153564 PMC5085171
  97. [102]Qu K. Zhang X. Lin T. Liu T. Wang Z. Liu S. Zhou L. Wei J. Chang H. Li K. Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation Sci. Rep. 7 2017 1692 28490741 PMC5431820
  98. [103]Zhu M. Huang Z. Zhu D. Zhou X. Shan X. Qi L.-W. Wu L. Cheng W. Zhu J. Zhang L. A panel of microRNA signature in serum for colorectal cancer diagnosis Oncotarget 8 2017 17081 17091 28177881 PMC5370024
  99. [104]Wang B. Zhang Q. The expression and clinical significance of circulating microRNA-21 in serum of five solid tumors J. Cancer Res. Clin. Oncol. 138 2012 1659 1666 22638884 PMC11824721
  100. [105]Zhang H. Li P. Ju H. Pesta M. Kulda V. Jin W. Cai M. Liu C. Wu H. Xu J. Diagnostic and prognostic value of microRNA-21 in colorectal cancer: an original study and individual participant data meta-analysis Cancer Epidemiol. Biomarkers Prev. 23 2014 2783 2792 25178983
  101. [106]Yaman Agaoglu F. Kovancilar M. Dizdar Y. Darendeliler E. Holdenrieder S. Dalay N. Gezer U. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer Tumour Biol. 32 2011 583 588 21274675
  102. [107]Jackson B.L. Grabowska A. Ratan H.L. MicroRNA in prostate cancer: functional importance and potential as circulating biomarkers BMC Cancer 14 2014 930 25496077 PMC4295407
  103. [108]Melbø-Jørgensen C. Ness N. Andersen S. Valkov A. Dønnem T. Al-Saad S. Kiselev Y. Berg T. Nordby Y. Bremnes R.M. Stromal expression of miR-21 predicts biochemical failure in prostate cancer patients with Gleason score 6 PLoS ONE 9 2014 e113039 25401698 PMC4234532
  104. [109]Zhou X. Wang X. Huang Z. Wang J. Zhu W. Shu Y. Liu P. Prognostic value of miR-21 in various cancers: an updating meta-analysis PLoS ONE 9 2014 e102413 25019505 PMC4097394
  105. [110]Vychytilova-Faltejskova P. Kiss I. Klusova S. Hlavsa J. Prochazka V. Kala Z. Mazanec J. Hausnerova J. Kren L. Hermanova M. miR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma Diagn. Pathol. 10 2015 38 25908274 PMC4407796
  106. [111]Du J. Zhang L. Analysis of salivary microRNA expression profiles and identification of novel biomarkers in esophageal cancer Oncol. Lett. 14 2017 1387 1394 28789354 PMC5529882
  107. [112]Yoshizawa J.M. Wong D.T.W. Salivary microRNAs and oral cancer detection Methods Mol. Biol. 936 2013 313 324 23007518 PMC3630337
  108. [113]Kutwin P. Konecki T. Borkowska E.M. Traczyk-Borszyńska M. Jabłonowski Z. Urine miRNA as a potential biomarker for bladder cancer detection—a meta-analysis Cent. European J. Urol. 71 2018 177 185 PMC6051360 30038807
  109. [114]Gao W. Lu X. Liu L. Xu J. Feng D. Shu Y. miRNA-21: a biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer Cancer Biol. Ther. 13 2012 330 340 22237007
  110. [115]Dong J. Zhao Y.-P. Zhou L. Zhang T.-P. Chen G. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells Arch. Med. Res. 42 2011 8 14 21376256
  111. [116]Wang P. Zhuang L. Zhang J. Fan J. Luo J. Chen H. Wang K. Liu L. Chen Z. Meng Z. The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL Mol. Oncol. 7 2013 334 345 23177026 PMC5528497
  112. [117]Liu B. Su F. Lv X. Zhang W. Shang X. Zhang Y. Zhang J. Serum microRNA-21 predicted treatment outcome and survival in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy combined with trastuzumab Cancer Chemother. Pharmacol. 84 2019 1039 1049 31482230
  113. [119]Zhang J. Jiao J. Cermelli S. Muir K. Jung K.H. Zou R. Rashid A. Gagea M. Zabludoff S. Kalluri R. Beretta L. miR-21 inhibition reduces liver fibrosis and prevents tumor development by inducing apoptosis of CD24+ progenitor cells Cancer Res. 75 2015 1859 1867 25769721 PMC4603420
  114. [121]Rodrigues P.M. Rodrigues C.M.P. Castro R.E. Modulation of liver steatosis by miR-21/PPARα Cell Death Discov. 4 2018 9 PMC6060160 30062058
  115. [122]Iorio M.V. Croce C.M. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review EMBO Mol. Med. 4 2012 143 159 22351564 PMC3376845
  116. [123]Li T. Li R.-S. Li Y.-H. Zhong S. Chen Y.-Y. Zhang C.-M. Hu M.-M. Shen Z.-J. miR-21 as an independent biochemical recurrence predictor and potential therapeutic target for prostate cancer J. Urol. 187 2012 1466 1472 22341810
  117. [124]Sicard F. Gayral M. Lulka H. Buscail L. Cordelier P. Targeting miR-21 for the therapy of pancreatic cancer Mol. Ther. 21 2013 986 994 23481326 PMC3666633
  118. [128]Haider B.A. Baras A.S. McCall M.N. Hertel J.A. Cornish T.C. Halushka M.K. A critical evaluation of microRNA biomarkers in non-neoplastic disease PLoS ONE 9 2014 e89565 24586876 PMC3935874
  119. [129]Witwer K.W. Circulating microRNA biomarker studies: pitfalls and potential solutions Clin. Chem. 61 2015 56 63 25391989
  120. [130]Tiberio P. Callari M. Angeloni V. Daidone M.G. Appierto V. Challenges in using circulating miRNAs as cancer biomarkers BioMed Res. Int. 2015 2015 731479 25874226 PMC4385632
  121. [131]Svoronos A.A. Engelman D.M. Slack F.J. OncomiR or tumor suppressor? The duplicity of microRNAs in cancer Cancer Res. 76 2016 3666 3670 27325641 PMC4930690
  122. [132]Buscaglia L.E.B. Li Y. Apoptosis and the target genes of microRNA-21 Chin. J. Cancer 30 2011 371 380 21627859 PMC3319771
  123. [133]Rupaimoole R. Han H.-D. Lopez-Berestein G. Sood A.K. MicroRNA therapeutics: principles, expectations, and challenges Chin. J. Cancer 30 2011 368 370 21627858 PMC4013410
  124. [134]Ren J. Kuang T.-H. Chen J. Yang J.-W. Liu Y.-X. The diagnostic and prognostic values of microRNA-21 in patients with gastric cancer: a meta-analysis Eur. Rev. Med. Pharmacol. Sci. 21 2017 120 130 28121346
  125. [135]Sekar D. Krishnan R. Thirugnanasambantham K. Rajasekaran B. Islam V.I.H. Sekar P. Significance of microRNA 21 in gastric cancer Clin. Res. Hepatol. Gastroenterol. 40 2016 538 545 27179559
  126. [136]Xu P. Zhu Y. Sun B. Xiao Z. Colorectal cancer characterization and therapeutic target prediction based on microRNA expression profile Sci. Rep. 6 2016 20616 26852921 PMC4745004
  127. [137]Medimegh I. Omrane I. Privat M. Uhrhummer N. Ayari H. Belaiba F. Benayed F. Benromdhan K. Mader S. Bignon I.-J. Elgaaied A.B. MicroRNAs expression in triple negative vs non triple negative breast cancer in Tunisia: interaction with clinical outcome PLoS ONE 9 2014 e111877 25369070 PMC4219794
  128. [138]Bica-Pop C. Cojocneanu-Petric R. Magdo L. Raduly L. Gulei D. Berindan-Neagoe I. Overview upon miR-21 in lung cancer: focus on NSCLC Cell. Mol. Life Sci. 75 2018 3539 3551 30030592 PMC11105782
  129. [139]Gu G.-L. Xu X.-L. Sun X.-T. Zhang J. Guo C.-F. Wang C.-S. Sun B. Guo G.-L. Ma K. Huang Y.-Y. Cardioprotective effect of microRNA-21 in murine myocardial infarction Cardiovasc. Ther. 33 2015 109 117 25809568
  130. [140]Yang L. Wang B. Zhou Q. Wang Y. Liu X. Liu Z. Zhan Z. MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7 Cell Death Dis. 9 2018 769 29991775 PMC6039462
  131. [141]Yuan J. Chen H. Ge D. Xu Y. Xu H. Yang Y. Gu M. Zhou Y. Zhu J. Ge T. Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7 Cell. Physiol. Biochem. 42 2017 2207 2219 28817807
  132. [142]Afonso M.B. Rodrigues P.M. Simão A.L. Gaspar M.M. Carvalho T. Borralho P. Bañales J.M. Castro R.E. Rodrigues C.M.P. miRNA-21 ablation protects against liver injury and necroptosis in cholestasis Cell Death Differ. 25 2018 857 872 29229992 PMC5943330
  133. [143]Namekawa T. Ikeda K. Horie-Inoue K. Inoue S. Application of prostate cancer models for preclinical study: advantages and limitations of cell lines, patient-derived xenografts, and three-dimensional culture of patient-derived cells Cells 8 2019 E74 30669516 PMC6357050
  134. [144]Zhou X. Wang T. Using the Wash U Epigenome Browser to examine genome-wide sequencing data Curr. Protoc. Bioinformatics 40 2012 10.10.1–10.10.14 PMC3643794 23255151
  135. [145]Löffler D. Brocke-Heidrich K. Pfeifer G. Stocsits C. Hackermüller J. Kretzschmar A.K. Burger R. Gramatzki M. Blumert C. Bauer K. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer Blood 110 2007 1330 1333 17496199
  136. [146]Kwak H.-J. Kim Y.-J. Chun K.-R. Woo Y.M. Park S.-J. Jeong J.-A. Jo S.H. Kim T.H. Min H.S. Chae J.S. Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas Oncogene 30 2011 2433 2442 21278789
  137. [147]Leite K.R.M. Reis S.T. Viana N. Morais D.R. Moura C.M. Silva I.A. Pontes J. Jr. Katz B. Srougi M. Controlling RECK miR21 promotes tumor cell invasion and is related to biochemical recurrence in prostate cancer J. Cancer 6 2015 292 301 25663948 PMC4317766
  138. [148]Gao M. Patel R. Ahmad I. Fleming J. Edwards J. McCracken S. Sahadevan K. Seywright M. Norman J. Sansom O. Leung H.Y. SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis EMBO Mol. Med. 4 2012 776 790 22649008 PMC3494076
  139. [149]Wietecha M.S. Chen L. Ranzer M.J. Anderson K. Ying C. Patel T.B. DiPietro L.A. Sprouty2 downregulates angiogenesis during mouse skin wound healing Am. J. Physiol. Heart Circ. Physiol. 300 2011 H459 H467 21076020 PMC3044050
  140. [150]Zhang X. Tang N. Hadden T.J. Rishi A.K. Akt, FoxO and regulation of apoptosis Biochim. Biophys. Acta 1813 2011 1978 1986 21440011
  141. [151]Moriishi T. Kawai Y. Komori H. Rokutanda S. Eguchi Y. Tsujimoto Y. Asahina I. Komori T. Bcl2 deficiency activates FoxO through Akt inactivation and accelerates osteoblast differentiation PLoS ONE 9 2014 e86629 24466179 PMC3896485
  142. [152]Memmott R.M. Dennis P.A. Akt-dependent and -independent mechanisms of mTOR regulation in cancer Cell. Signal. 21 2009 656 664 19166931 PMC2650010
  143. [153]Zhou H. Huang S. Role of mTOR signaling in tumor cell motility, invasion and metastasis Curr. Protein Pept. Sci. 12 2011 30 42 21190521 PMC3410744
  144. [154]Oh J. Takahashi R. Kondo S. Mizoguchi A. Adachi E. Sasahara R.M. Nishimura S. Imamura Y. Kitayama H. Alexander D.B. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis Cell 107 2001 789 800 11747814
  145. [155]Takahashi C. Sheng Z. Horan T.P. Kitayama H. Maki M. Hitomi K. Kitaura Y. Takai S. Sasahara R.M. Horimoto A. Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK Proc. Natl. Acad. Sci. USA 95 1998 13221 13226 9789069 PMC23764
  146. [156]Miller M.A. Sullivan R.J. Lauffenburger D.A. Molecular pathways: receptor ectodomain shedding in treatment, resistance, and monitoring of cancer Clin. Cancer Res. 23 2017 623 629 27895032 PMC5290119
  147. [157]Campbell K.J. Tait S.W.G. Targeting BCL-2 regulated apoptosis in cancer Open Biol. 8 2018 180002 29769323 PMC5990650
  148. [158]Shen L. Ling M. Li Y. Xu Y. Zhou Y. Ye J. Pang Y. Zhao Y. Jiang R. Zhang J. Liu Q. Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation PLoS ONE 8 2013 e57652 23469214 PMC3585869

Cited by

Sorted by citations

Authors
Bautista-Sánchez, D., Arriaga-Canon, C., Pedroza-Torres, A., De La Rosa-Velázquez, I. A., González-Barrios, R., Contreras-Espinosa, L., Montiel-Manríquez, R., Castro-Hernández, C., Fragoso-Ontiveros, V., Álvarez-Gómez, R. M., & Herrera, L. A.
Affiliations
  • Instituto Nacional de Cancerología (MX)
  • National Institute of Genomic Medicine (MX)
Corresponding author
Herrera, Luis A.
ORCID
Venue
Molecular Therapy Nucleic Acids
Publisher
Elsevier BV
Published
2020-06
Volume
20
Pages
409-420
ISSN
2162-2531 (ISSN-L)
DOI
10.1016/j.omtn.2020.03.003
PMC
PMC7118281
OpenAlex
W3010881000
Cited by
549
References
7
Citations by year
2026: 87 · 2025: 117 · 2024: 112 · 2023: 72 · 2022: 83 · 2021: 59 · 2020: 19
FWCI
6.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
National Cancer Institute of Mexico
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
miR-21, microRNA, tumor markers, oncogenic microRNA, RNA therapeutics, anti-miR oligonucleotides, PTEN, PDCD4, RECK, STAT3, tumor suppression, metastasis, precision medicine, glioma, breast cancer, colorectal cancer

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review