METTL3 promotes proliferation and migration of colorectal cancer cells by increasing SNHG1 stability

Xu,Yeqiu; Xu,Yeqiu; Bao,Yuxin; Bao,Yuxin; Qiu,Guanzhen; Qiu,Guanzhen; Ye,Huinan; Ye,Huinan; He,Ming; He,Ming; Wei,Xilin; Wei,Xilin

doi:10.3892/mmr.2023.13104

METTL3 promotes proliferation and migration of colorectal cancer cells by increasing SNHG1 stability

Authors:
- Yeqiu Xu
- Yuxin Bao
- Guanzhen Qiu
- Huinan Ye
- Ming He
- Xilin Wei
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Affiliations: Fourth Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China, Department of Medical Oncology, Cancer Hospital of Dalian University of Technology/Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110024, P.R. China, Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110024, P.R. China, Third Department of General Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China
Published online on: September 26, 2023 https://doi.org/10.3892/mmr.2023.13104
Article Number: 217
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

N⁶‑methyladenosine (m6A) serves an essential role in RNA modulation and is implicated in multiple malignancies, including colorectal cancer (CRC). Methyltransferase‑like 3 (METTL3) is an important writer in m6A modification, however its role in CRC in modifying small nucleolar RNA host gene 1 (SNHG1), an oncogenic long noncoding RNA, remains unclear. In the present study, METTL3 expression in CRC was assessed using online bioinformatics analysis, immunohistochemistry staining, western blotting, reverse transcription (RT)‑quantitative PCR (qPCR) and cell transfections. Cell proliferation, migration and invasion were determined using functional Cell Counting Kit‑8 (CCK‑8) and Transwell assays. SNHG1 expression in CRC was evaluated using online bioinformatics analysis and RT‑qPCR. Methylated RNA immunoprecipitation qPCR was performed to assess m6A modification changes of SNHG1 mRNA. The present study demonstrated that METTL3 is upregulated in CRC tissues and cell lines. Moreover, METTL3 expression was associated with several unfavourable clinical features in patients with CRC, including the stage of lymph node metastases and overall survival. Functional Transwell and CCK‑8 assays demonstrated that knockdown of METTL3 suppressed CRC cell proliferation and migration. Furthermore, METTL3 was positively correlated with SNHG1 in CRC tissue, as indicated by analysis of data from The Cancer Genome Atlas. Mechanistically, SNHG1 contains 18 m6A modification sites. Through cell transfections and actinomycin D assays, the present study found that METTL3‑mediated m6A modification at these sites enhances the stability of SNHG1 in CRC cells. Finally, it was demonstrated that SNHG1 knockdown partially diminished the facilitative effect of METTL3 on CRC cell migration and proliferation. The present study concluded that METTL3, a potential biomarker for assessing overall survival and metastasis in CRC, may serve as an oncogene, promote SNHG1 m6A modification, improve the stability of SNHG1 and enhance SNHG1‑mediated oncogenic function in CRC.

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