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Article Open Access

m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation

  • Authors:
    • Jihao Xu
    • Qikui Chen
    • Kuangyi Tian
    • Rongrong Liang
    • Ting Chen
    • Aiyu Gong
    • Nicholas W. Mathy
    • Tao Yu
    • Xianming Chen
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 973-986
    |
    Published online on: June 26, 2020
       https://doi.org/10.3892/or.2020.7665
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Abstract

N6‑methyladenosine (m6A) RNA modification maintained by N6‑methyltransferases and demethylases is involved in multiple biological functions. Methyltransferase like 3 (METTL3) is a major N6‑methyltransferase. However, the role of METTL3 and its installed m6A modification in colorectal tumorigenesis remains to be fully elucidated. METTL3 is highly expressed as indicated in colorectal cancer samples in the TCGA and Oncomine databases, implying its potential role in colon tumorigenesis. SW480 cell line with stable METTL3 knockout (METTL3‑KO) was generated using CRISPR/Cas9 and were confirmed by the loss of METTL3 expression and suppression of m6A modification. The proliferation of METTL3‑KO cells was significantly inhibited compared with that of control cells. METTL3‑KO decreased the decay rate of suppressor of cytokine signaling 2 (SOCS2) RNA, resulting in elevated SOCS2 protein expression. m6A‑RNA immunoprecipitation‑qPCR (MeRIP‑qPCR) revealed that SOCS2 mRNA was targeted by METTL3 for m6A modification. Similar to METTL3‑KO SW480 cells, SW480 cells treated with 3‑deazaadenosine, an RNA methylation inhibitor, exhibited elevated SOCS2 protein expression. Increased levels of SOCS2 in METTL3‑KO SW480 cells were associated with decreased expression of leucine‑rich repeat‑containing G protein‑coupled receptor 5 (LGR5), contributing to the inhibition of cell proliferation. The underlying associations among METTL3, SOCS2, and LGR5 were further confirmed in SW480 cells transfected with si‑METTL3 and in tumor samples from patients with colorectal cancer. Taken together, our data demonstrate that an increased level of METTL3 may maintain the tumorigenicity of colon cancer cells by suppressing SOCS2.
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Copy and paste a formatted citation
Spandidos Publications style
Xu J, Chen Q, Tian K, Liang R, Chen T, Gong A, Mathy NW, Yu T and Chen X: m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncol Rep 44: 973-986, 2020.
APA
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A. ... Chen, X. (2020). m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncology Reports, 44, 973-986. https://doi.org/10.3892/or.2020.7665
MLA
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A., Mathy, N. W., Yu, T., Chen, X."m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation". Oncology Reports 44.3 (2020): 973-986.
Chicago
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A., Mathy, N. W., Yu, T., Chen, X."m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation". Oncology Reports 44, no. 3 (2020): 973-986. https://doi.org/10.3892/or.2020.7665
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Chen Q, Tian K, Liang R, Chen T, Gong A, Mathy NW, Yu T and Chen X: m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncol Rep 44: 973-986, 2020.
APA
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A. ... Chen, X. (2020). m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation. Oncology Reports, 44, 973-986. https://doi.org/10.3892/or.2020.7665
MLA
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A., Mathy, N. W., Yu, T., Chen, X."m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation". Oncology Reports 44.3 (2020): 973-986.
Chicago
Xu, J., Chen, Q., Tian, K., Liang, R., Chen, T., Gong, A., Mathy, N. W., Yu, T., Chen, X."m6A methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation". Oncology Reports 44, no. 3 (2020): 973-986. https://doi.org/10.3892/or.2020.7665
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