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METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma

Open access
Li, Ting, Hu, Pei-Shan, Zuo, Zhixiang, Lin, Jin-Fei, Li, Xingyang, Wu, Qi-Nian, Chen, Zhan-Hong, Zeng, Zhao-Lei, Wang, Feng, Zheng, Jian, Chen, Demeng, Li, Bo, Kang, Tie-Bang, Xie, Dan, Lin, Dongxin, Ju, Huai-Qiang, Xu, Rui-Hua·2019·Molecular Cancer
DOI 10.1186/s12943-019-1038-7
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Abstract

Abstract Background Colorectal carcinoma (CRC) is one of the most common malignant tumors, and its main cause of death is tumor metastasis. RNA N 6 -methyladenosine (m 6 A) is an emerging regulatory mechanism for gene expression and methyltransferase-like 3 (METTL3) participates in tumor progression in several cancer types. However, its role in CRC remains unexplored. Methods Western blot, quantitative real-time PCR (RT-qPCR) and immunohistochemical (IHC) were used to detect METTL3 expression in cell lines and patient tissues. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL3. The biological functions of METTL3 were investigated in vitro and in vivo. RNA pull-down and RNA immunoprecipitation assays were conducted to explore the specific binding of target genes. RNA stability assay was used to detect the half-lives of the downstream genes of METTL3. Results Using TCGA database, higher METTL3 expression was found in CRC metastatic tissues and was associated with a poor prognosis. MeRIP-seq revealed that SRY (sex determining region Y)-box 2 (SOX2) was the downstream gene of METTL3. METTL3 knockdown in CRC cells drastically inhibited cell self-renewal, stem cell frequency and migration in vitro and suppressed CRC tumorigenesis and metastasis in both cell-based models and PDX models. Mechanistically, methylated SOX2 transcripts, specifically the coding sequence (CDS) regions, were subsequently recognized by the specific m 6 A “reader”, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), to prevent SOX2 mRNA degradation. Further, SOX2 expression positively correlated with METTL3 and IGF2BP2 in CRC tissues. The combined IHC panel, including “writer”, “reader”, and “target”, exhibited a better prognostic value for CRC patients than any of these components individually. Conclusions Overall, our study revealed that METTL3, acting as an oncogene, maintained SOX2 expression through an m 6 A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in CRC.

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Research works printed but not linked: 37

  1. Xu RH, Muro K, Morita S, Iwasa S, Han SW, Wang W, Kotaka M, Nakamura M, Ahn JB, Deng YH, et al. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2018;19:660–71. · DOI
  2. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10. · DOI · Paper page
  3. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5. · DOI · Paper page
  4. Hu PS, Xia QS, Wu F, Li DK, Qi YJ, Hu Y, Wei ZZ, Li SS, Tian NY, Wei QF, et al. NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma. Oncogene. 2017;36:4706–18. · DOI
  5. Hao X, Luo H, Krawczyk M, Wei W, Wang W, Wang J, Flagg K, Hou J, Zhang H, Yi S, et al. DNA methylation markers for diagnosis and prognosis of common cancers. Proc Natl Acad Sci U S A. 2017;114:7414–9. · DOI · Paper page
  6. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater. 2017;16:1155–61. · DOI · Paper page
  7. Deng X, Su R, Feng X, Wei M, Chen J. Role of N (6)-methyladenosine modification in cancer. Curr Opin Genet Dev. 2018;48:1–7. · DOI · Paper page
  8. Fustin JM, Doi M, Yamaguchi Y, Hida H, Nishimura S, Yoshida M, Isagawa T, Morioka MS, Kakeya H, Manabe I, Okamura H. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell. 2013;155:793–806. · DOI · Paper page
  9. Lin S, Choe J, Du P, Triboulet R, Gregory RI. The m(6)a methyltransferase METTL3 promotes translation in human Cancer cells. Mol Cell. 2016;62:335–45. · DOI · Paper page
  10. Chen T, Hao Y-J, Zhang Y, Li M-M, Wang M, Han W, Wu Y, Lv Y, Hao J, Wang L, et al. m6A RNA methylation is regulated by MicroRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 2015;16:289–301. · DOI · Paper page
  11. Li Z, Weng H, Su R, Weng X, Zuo Z, Li C, Huang H, Nachtergaele S, Dong L, Hu C, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N(6)-Methyladenosine RNA demethylase. Cancer Cell. 2017;31:127–41. · DOI · Paper page
  12. Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z, Sheng W, Xu C, Chen H, Ouyang J, Wang S, et al. RNA m(6)a methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017;543:573–6. · DOI · Paper page
  13. Weng H, Huang H, Wu H, Qin X, Zhao BS, Dong L, Shi H, Skibbe J, Shen C, Hu C, et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes Leukemogenesis via mRNA m(6)a modification. Cell Stem Cell. 2018;22:191–205 e199. · DOI · Paper page
  14. Zhang S, Zhao BS, Zhou A, Lin K, Zheng S, Lu Z, Chen Y, Sulman EP, Xie K, Bogler O, et al. m(6)a demethylase ALKBH5 maintains Tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell. 2017;31:591–606 e596. · DOI · Paper page
  15. Deng X, Su R, Weng H, Huang H, Li Z, Chen J. RNA N(6)-methyladenosine modification in cancers: current status and perspectives. Cell Res. 2018;28:507–17. · DOI · Paper page
  16. Chen M, Wei L, Law CT, Tsang FH, Shen J, Cheng CL, Tsang LH, Ho DW, Chiu DK, Lee JM, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology. 2018;67:2254–70. · DOI · Paper page
  17. Ju HQ, Lu YX, Chen DL, Zuo ZX, Liu ZX, Wu QN, Mo HY, Wang ZX, Wang DS, Pu HY, et al. Modulation of redox homeostasis by inhibition of MTHFD2 in colorectal Cancer: mechanisms and therapeutic implications. J Natl Cancer Inst. 2018. https://doi.org/10.1093/jnci/djy160. · DOI · Paper page
  18. Dominissini D, Moshitch-Moshkovitz S, Salmon-Divon M, Amariglio N, Rechavi G. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing. Nat Protoc. 2013;8:176–89. · DOI · Paper page
  19. Witty JP, McDonnell S, Newell KJ, Cannon P, Navre M, Tressler RJ, Matrisian LM. Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Res. 1994;54:4805–12.
  20. Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, Delatte B, Caauwe A, Lenglez S, Nkusi E, et al. SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma. Nature. 2014;511:246–50. · DOI · Paper page
  21. Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, Goodrich MM, Labbe DP, Gomez EC, Wang J, et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science. 2017;355:78–83. · DOI · Paper page
  22. Xu Z, Zeng X, Xu J, Xu D, Li J, Jin H, Jiang G, Han X, Huang C. Isorhapontigenin suppresses growth of patient-derived glioblastoma spheres through regulating miR-145/SOX2/cyclin D1 axis. Neuro-Oncology. 2016;18:830–9. · doi:10.1093/neuonc/nov298
  23. Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol. 2005;25:6031–46. · DOI · Paper page
  24. Park SB, Seo KW, So AY, Seo MS, Yu KR, Kang SK, Kang KS. SOX2 has a crucial role in the lineage determination and proliferation of mesenchymal stem cells through Dickkopf-1 and c-MYC. Cell Death Differ. 2012;19:534–45. · DOI
  25. Lu YX, Ju HQ, Liu ZX, Chen DL, Wang Y, Zhao Q, Wu QN, Zeng ZL, Qiu HB, Hu PS, et al. ME1 regulates NADPH homeostasis to promote gastric Cancer growth and metastasis. Cancer Res. 2018;78:1972–85. · DOI
  26. Cai X, Wang X, Cao C, Gao Y, Zhang S, Yang Z, Liu Y, Zhang X, Zhang W, Ye L. HBXIP-elevated methyltransferase METTL3 promotes the progression of breast cancer via inhibiting tumor suppressor let-7g. Cancer Lett. 2018;415:11–9. · DOI · Paper page
  27. Cui Q, Shi H, Ye P, Li L, Qu Q, Sun G, Sun G, Lu Z, Huang Y, Yang CG, et al. M(6)a RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep. 2017;18:2622–34. · DOI · Paper page
  28. Vu LP, Pickering BF, Cheng Y, Zaccara S, Nguyen D, Minuesa G, Chou T, Chow A, Saletore Y, MacKay M, et al. The N(6)-methyladenosine (m(6)a)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med. 2017;23:1369–76. · DOI · Paper page
  29. Visvanathan A, Patil V, Arora A, Hegde AS, Arivazhagan A, Santosh V, Somasundaram K. Essential role of METTL3-mediated m(6)a modification in glioma stem-like cells maintenance and radioresistance. Oncogene. 2018;37:522–33. · DOI · Paper page
  30. Ma JZ, Yang F, Zhou CC, Liu F, Yuan JH, Wang F, Wang TT, Xu QG, Zhou WP, Sun SH. METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N(6) -methyladenosine-dependent primary MicroRNA processing. Hepatology. 2017;65:529–43. · DOI · Paper page
  31. Ju HQ, Lu YX, Chen DL, Tian T, Mo HY, Wei XL, Liao JW, Wang F, Zeng ZL, Pelicano H, et al. Redox regulation of stem-like cells though the CD44v-xCT Axis in colorectal Cancer: mechanisms and therapeutic implications. Theranostics. 2016;6:1160–75. · DOI
  32. de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD, Hung J, Anderson JE, Storm EE, Modrusan Z, Koeppen H, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature. 2017;543:676–80. · DOI · Paper page
  33. Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138:2151–62. · DOI · Paper page
  34. Justilien V, Walsh MP, Ali SA, Thompson EA, Murray NR, Fields AP. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate hedgehog signaling in lung squamous cell carcinoma. Cancer Cell. 2014;25:139–51. · DOI · Paper page
  35. Cao J, Mu Q, Huang H. The roles of insulin-like growth factor 2 mRNA-binding protein 2 in Cancer and Cancer stem cells. Stem Cells Int. 2018;2018:4217259.
  36. Degrauwe N, Schlumpf TB, Janiszewska M, Martin P, Cauderay A, Provero P, Riggi N, Suva ML, Paro R, Stamenkovic I. The RNA binding protein IMP2 preserves glioblastoma stem cells by preventing let-7 target gene silencing. Cell Rep. 2016;15:1634–47. · DOI · Paper page
  37. Janiszewska M, Suva ML, Riggi N, Houtkooper RH, Auwerx J, Clement-Schatlo V, Radovanovic I, Rheinbay E, Provero P, Stamenkovic I. Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes Dev. 2012;26:1926–44. · DOI · Paper page

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Metadata

Authors
Li, T., Hu, P.-S., Zuo, Z., Lin, J.-F., Li, X., Wu, Q.-N., Chen, Z.-H., Zeng, Z.-L., Wang, F., Zheng, J., Chen, D., Li, B., Kang, T.-B., Xie, D., Lin, D., Ju, H.-Q., & Xu, R.-H.
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2019-06-24
Volume
18
Issue
1
Pages
112-112
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-019-1038-7
OpenAlex
W2951746943
Cited by
799
References
5
FWCI
30.08
Type
journal article
Language
en
Update notices
correction (2026-09-05)
Open access
gold
Licence
Funders
National Natural Science Foundation of China (81871951, 81772614)

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CoChat. (2026). Citation check: METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma. https://app.cochat.ai/papers/10.1186/s12943-019-1038-7
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Li, T., Hu, P.-S., Zuo, Z., Lin, J.-F., Li, X., Wu, Q.-N., Chen, Z.-H., Zeng, Z.-L., Wang, F., Zheng, J., Chen, D., Li, B., Kang, T.-B., Xie, D., Lin, D., Ju, H.-Q., & Xu, R.-H. (2019). METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma. Molecular Cancer. https://doi.org/10.1186/s12943-019-1038-7

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