Int J Biol Sci 2022; 18(7):3048-3065. doi:10.7150/ijbs.70630 This issue

Research Paper

RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis

Ke Shi1,2,3*, Shuaixi Yang1,3*, Chen Chen1,3,4, Bo Shao1,3, Yaxin Guo4,5,6, Xiaoke Wu1,7, Luyang Zhao4,5,6, Xiuxiu Yang1,3, Qiuge Zhang2,7, Weitang Yuan1, Zhenqiang Sun1,3✉

1. Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
2. Department of Plastic Surgery, Central South University Third Xiangya Hospital, Changsha 410013, Hunan, China.
3. Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China.
4. School of Life Science, Zhengzhou University, Zhengzhou, 450001, Henan, China.
5. School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450002, Henan, China.
6. Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China.
7. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
8. Department of Geriatric Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
*These authors contributed equally to this work.

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Citation:
Shi K, Yang S, Chen C, Shao B, Guo Y, Wu X, Zhao L, Yang X, Zhang Q, Yuan W, Sun Z. RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis. Int J Biol Sci 2022; 18(7):3048-3065. doi:10.7150/ijbs.70630. Available from https://www.ijbs.com/v18p3048.htm

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Abstract

Graphic abstract

Long noncoding RNAs (lncRNAs) regulate multiple biological effects in cancers. Recently, RNA methylation has been found to modify not only coding RNAs but also some noncoding RNAs. How RNA methylation affects lncRNAs to affect colorectal cancer (CRC) progression remains elusive. The expression of LINC01559 was explored through RNA sequencing, quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). The preliminary exploration of its function was performed using Western blotting (WB) and immunohistochemistry (IHC). Functional experiments in vitro and in vivo were conducted to explore the biological functions of LINC01559 in CRC. The LINC01559/miR-106-5p/PTEN axis was verified through fluorescence in situ hybridization (FISH), luciferase assays, and rescue experiments. RIP-sequencing, m6A RNA immunoprecipitation (MeRIP) assays and bioinformatic analysis were conducted to determine the upstream mechanism of LINC01559. The results showed that LINC01559 was downregulated in CRC compared with normal controls. Lower expression of LINC01559 in CRC patients predicted a poor prognosis. In addition, PTEN was found to be positively correlated with LINC01559, and miR-106b-5p could be the link between LINC01559 and PTEN. Then, silencing LINC01559 restored the malignant phenotype of CRC cells, while cotransfection of miR-106b-5p inhibitor neutralized this effect. Mechanistically, we found abundant m6A modification sites on LINC01559. Then, we uncovered these sites as potential targets of METTL3 through experiments in vivo. The results revealed a negative functional regulation of the LINC01559/miR-106b-5p/PTEN axis in CRC progression and explored a new mechanism of METTL3-mediated m6A modification on LINC01559. These results elucidate a novel potential therapeutic target for CRC treatment.

Keywords: LINC01559, PTEN, METTL3, colorectal cancer