Cited by 305Cancer-related molecular mechanisms researchMicroRNA in disease regulationCircular RNAs in diseases

Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21

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Zhang, Jun, Yao, Tingting, Wang, Yaxian, Yu, Jin, Liu, Yunyun, Lin, Zhongqiu·2016·Cancer Biology & Therapy

Abstract

Recent research has found that long noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in cervical cancer remains unexplored. Therefore, we aimed to investigate the biological function of maternally expressed gene 3 (MEG3), a cancer-related lncRNA, and its underlying mechanism in cervical cancer. In this study, MEG3 expression of 108 patients' cervical cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR analysis (qRT-PCR), and the functional effect of MEG3 was determined in vitro assays. We observed that MEG3 was downregulated in cervical cancer tissues, compared to the adjacent normal tissues, and was negatively related with FIGO stages, tumor size, lymphatic metastasis, HR-HPV infection and the expression of homo sapiens microRNA-21 (miR-21). Furthermore, we focused on the function and molecular mechanism of MEG3, finding that overexpression of MEG3 reduced the level of miR-21-5p expression, causing inhibition of proliferation and increased apoptosis in cervical cancer cells. In summary, our findings indicate that MEG3 function as a tumor suppressor by regulating miR-21-5p, resulting in the inhibition of tumor growth in cervical cancer. As a result, this study improves our understanding of the function of MEG3 in cervical cancer and will help to provide new potential target sites for cervical cancer treatment.

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  • MEG3 serves as a ceRNA for miR-21 to regulate cell proliferation or apoptosis in some tumors.

    “More significantly, studies have revealed that MEG3 serves as a ceRNA for miR-21 to regulate cell proliferation or apoptosisin in some tumors34,35, but whether MEG3 competes with mRNA for miR-21 in ischemia and contributes to ischemic neuronal death remained unexplored.”

    From Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway (2017) · cites this paper as [34]

    The Results and Discussion (page not provided) report that MEG3 regulates miR-21-5p and affects proliferation and apoptosis in cervical cancer cells. They do not establish that MEG3 acts as a competing endogenous RNA (ceRNA) for miR-21; the Discussion says the exact mechanism of their interaction requires further study. (LLM, conf=0.88)

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Research works printed but not linked: 24

  1. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, Naghavi M. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011; 378:1461- 84; PMID:21924486; http://dx.doi.org/10.1016/S0140-6736(11)61351-2 · DOI · Paper page
  2. Tewari KS, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014; 370(8):734-43; PMID:24552320; http://dx.doi.org/10.1056/ NEJMoa1309748 · DOI
  3. Zhao YB, Wang JH, Chen XX, Wu YZ, Wu Q. Values of three different preoperative regimens in comprehensive treatment for young patients with stage Ib2 cervical cancer. Asian Pac J Cancer Prev 2012; 13 (4):1487-9; PMID:22799353; http://dx.doi.org/10.7314/ APJCP.2012.13.4.1487 · DOI
  4. Ponting CP, Oliver PL, Reik W. Evolution and functions of long non- coding RNAs. Cell 2009; 136(4):629-41; PMID:19239885; http://dx. doi.org/10.1016/j.cell.2009.02.006 · DOI
  5. Lujambio A, Portela A, Liz J, Melo SA, Rossi S, Spizzo R, Croce CM, Calin GA, Esteller M. CpG island hypermethylation-associated silenc- ing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene 2010; 29(48):6390-401; PMID:20802525; http://dx.doi.org/10.1038/onc.2010.361 · DOI
  6. Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 2009; 23(13):1494-504; PMID:19571179; http://dx.doi.org/10.1101/gad.1800909 · DOI
  7. Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP, Hou YY. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer 2013; 13:461; PMID:24098911; http://dx.doi.org/10.1186/1471-2407-13-461 · DOI
  8. Sun M, Xia R, Jin F, Xu T, Liu Z, De W, Liu X. Downregulated long noncoding RNA MEG3 is associated with poor prognosis and pro- motes cell proliferation in gastric cancer. Tumor Biol 2014; 35 (2):1065-73; PMID:24006224; http://dx.doi.org/10.1007/s13277-013- 1142-z · DOI
  9. Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, Weng H, Shu YJ, Liu TY, Jiang L, et al. MALAT1 promotes the proliferation and metas- tasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Figure 9. MiR-21-5p mediated the effects of MEG3 on regulating P53 and cleaved caspase 3 protein levels. (A) The level of p53 and cleaved caspase 3 protein was decreased in pcDNA-MEG3 C miR-21-5p mimic group. (B) The level of p53 and cleaved caspase 3 protein was increased in si-MEG3 C miR-21-5p inhibitor groups. Cancer Biol Ther 2014; 15(6):806-14; PMID:24658096; http://dx.doi. org/10.4161/cbt.28584 · DOI
  10. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and func- tion. Cell 2004; 116(2):281-97; PMID:14744438; http://dx.doi.org/ 10.1016/S0092-8674(04)00045-5 · DOI
  11. Yao T, Lin Z. MiR-21 is involved in cervical squamous cell tumor- igenesis and regulates CCL20. Biochim Biophys Acta 2012; 1822 (2):248-60; PMID:22001440; http://dx.doi.org/10.1016/j.bbadis. 2011.09.018 · DOI
  12. Yao Q, Xu H, Zhang QQ, Zhou H, Qu LH. MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells. Biochem Bio- phys Res Commun 2009; 388(3):539-42; PMID:19682430; http://dx. doi.org/10.1016/j.bbrc.2009.08.044 · DOI
  13. Shishodia G, Verma G, Srivastava Y, Mehrotra R, Das BC, Bharti AC. Deregulation of microRNAs Let-7a and miR-21 mediate aberrant STAT3 signaling during human papillomavirus-induced cervical carci- nogenesis: role of E6 oncoprotein. BMC Cancer 2014; 14:996; PMID:25539644; http://dx.doi.org/10.1186/1471-2407-14-996 · DOI
  14. Liu S, Song L, Zhang L, Zeng S, Gao F. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1. Biochem Biophys Res Commun 2015; 459(4):679-85; PMID:25769949; http://dx.doi.org/10.1016/j.bbrc.2015.03.004 · DOI
  15. Collins LJ. The RNA infrastructure: an introduction to ncRNA net- works. Adv Exp Med Biol 2011; 722: 1-19; PMID:21915779; http://dx. doi.org/10.1007/978-1-4614-0332-6_1 · DOI
  16. Wang P, Liu YH, Yao YL, Li Z, Li ZQ, Ma J, Xue YX. Long non-coding RNA CASC2 suppresses malignancy in human gliomas by miR-21. Cell Signal 2015; 27(2):275-82; PMID:25446261; http://dx.doi.org/ 10.1016/j.cellsig.2014.11.011 · DOI
  17. Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, Wu F, Mo YY. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ 2013; 20(11):1558-68; PMID:23933812; http://dx.doi.org/10.1038/ cdd.2013.110 · DOI
  18. Qin R, Chen Z, Ding Y, Hao J, Hu J, Guo F. Long non-coding RNA MEG3 inhibits the proliferation of cervical carcinoma cells through the induction of cell cycle arrest and apoptosis. Neoplasma 2013; 60 (5):486-92; PMID:23790166; http://dx.doi.org/10.4149/neo_2013_063 · DOI
  19. Leucci E, Patella F, Waage J, Holmstrøm K, Lindow M, Porse B, Kaup- pinen S, Lund AH. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep 2013; 3:2535; PMID:23985560; http://dx.doi.org/10.1038/srep02535 · DOI
  20. Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L, Wu M, Xiong J, Guo X, Liu H. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 2013; 25(1):69-80; PMID:23541921; http://dx.doi.org/10.1016/j. devcel.2013.03.002 · DOI
  21. Faghihi MA, Zhang M, Huang J, Modarresi F, Van der Brug MP, Nalls MA, Cookson MR, St-Laurent G 3rd, Wahlestedt C. Evidence for natu- ral antisense transcript-mediated inhibition of microRNA function. Genome Biol 2010; 11(5):R56; PMID:20507594; http://dx.doi.org/ 10.1186/gb-2010-11-5-r56 · DOI
  22. Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, Reik W. The H19 lincRNA is a developmental reservoir of miR-675 that sup- presses growth and Igf1r. Nat Cell Biol 2012; 14(7):659-65; PMID:22684254; http://dx.doi.org/10.1038/ncb2521 · DOI
  23. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A. Activation of p53 by meg3 non-coding RNA. J Biol Chem 2007; 282(34):24731-42; PMID:17569660; http:// dx.doi.org/10.1074/jbc.M702029200 · DOI
  24. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008; 283(2) 1026-33; PMID:17991735; http://dx.doi.org/10.1074/jbc.M707224200 · DOI · Paper page

Cited by

Sorted by citations

Authors
Zhang, J., Yao, T., Wang, Y., Yu, J., Liu, Y., & Lin, Z.
Affiliations
Sun Yat-sen University (CN)
Corresponding author
Lin, Zhongqiu
Venue
Cancer Biology & Therapy
Published
2015-11-17
Volume
17
Issue
1
Pages
104-113
ISSN
  • 1538-4047 (ISSN-L)
  • 1555-8576
OpenAlex
W2174891444
Cited by
305
References
3
Citations by year
2026: 3 · 2025: 11 · 2024: 14 · 2023: 27 · 2022: 18 · 2021: 30 · 2020: 49 · 2019: 49 · 2018: 50 · 2017: 43 · 2016: 8 · 2015: 1
FWCI
11.24
Type
journal article
Language
en
Open access
Locations
  • Cancer Biology & Therapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81572575)
  • Natural Science Foundation of Guangdong Province (2014A030313109)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
Keywords
MEG3, long non-coding RNA, cervical cancer, miR-21-5p, tumor suppressor, cell proliferation, apoptosis, microRNA regulation, HPV infection, lymph node metastasis, FIGO stage
MeSH terms
Aged, Uterine Cervical Neoplasms, Female, Humans, Lymphatic Metastasis, Middle Aged, Gene Expression Regulation, Neoplastic, Apoptosis, DNA Methylation, MicroRNAs, Cell Line, Tumor, Cell Proliferation, RNA, Long Noncoding

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