PMID- 35541914 OWN - NLM STAT- MEDLINE DCOM- 20220512 LR - 20220716 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 18 IP - 7 DP - 2022 TI - RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis. PG - 3048-3065 LID - 10.7150/ijbs.70630 [doi] AB - 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. CI - (c) The author(s). FAU - Shi, Ke AU - Shi K AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Department of Plastic Surgery, Central South University Third Xiangya Hospital, Changsha 410013, Hunan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Yang, Shuaixi AU - Yang S AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Chen, Chen AU - Chen C AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. AD - School of Life Science, Zhengzhou University, Zhengzhou, 450001, Henan, China. FAU - Shao, Bo AU - Shao B AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Guo, Yaxin AU - Guo Y AD - School of Life Science, Zhengzhou University, Zhengzhou, 450001, Henan, China. AD - School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450002, Henan, China. AD - Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Wu, Xiaoke AU - Wu X AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhao, Luyang AU - Zhao L AD - School of Life Science, Zhengzhou University, Zhengzhou, 450001, Henan, China. AD - School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450002, Henan, China. AD - Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Yang, Xiuxiu AU - Yang X AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhang, Qiuge AU - Zhang Q AD - Department of Plastic Surgery, Central South University Third Xiangya Hospital, Changsha 410013, Hunan, China. AD - Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Yuan, Weitang AU - Yuan W AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Sun, Zhenqiang AU - Sun Z AD - Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. AD - Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220424 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 2.1.1.- (Methyltransferases) RN - EC 2.1.1.62 (METTL3 protein, human) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - *Colorectal Neoplasms/metabolism MH - Gene Expression Regulation, Neoplastic/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Methylation MH - Methyltransferases/genetics MH - *MicroRNAs/genetics/metabolism MH - PTEN Phosphohydrolase/genetics/metabolism MH - *RNA, Long Noncoding/genetics/metabolism PMC - PMC9066122 OTO - NOTNLM OT - LINC01559 OT - METTL3 OT - PTEN OT - colorectal cancer COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2022/05/12 06:00 MHDA- 2022/05/14 06:00 PMCR- 2022/01/01 CRDT- 2022/05/11 04:05 PHST- 2021/12/31 00:00 [received] PHST- 2022/04/09 00:00 [accepted] PHST- 2022/05/11 04:05 [entrez] PHST- 2022/05/12 06:00 [pubmed] PHST- 2022/05/14 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - ijbsv18p3048 [pii] AID - 10.7150/ijbs.70630 [doi] PST - epublish SO - Int J Biol Sci. 2022 Apr 24;18(7):3048-3065. doi: 10.7150/ijbs.70630. eCollection 2022.