PMID- 34850551 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220531 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 26 IP - 2 DP - 2022 Jan TI - ALKBH5-mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9. PG - 385-398 LID - 10.1111/jcmm.17091 [doi] AB - It has been shown that N6-methyladenosine (m6A) modification is involved in the development of complex human diseases, especially in the development of cancer. Our research investigated the role and mechanism of the m6A modification of lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) in Laryngeal squamous cell carcinoma (LSCC) progression. Microarray analysis was used to quantitatively detect the m6A apparent transcriptional modification level of lncRNA in LSCC tissue. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR), in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) were used to examine the m6A modification and expression of KCNQ1OT1. In addition, in vivo and in vitro experiments have tested the effects of KCNQ1OT1 knockdown on the proliferation, invasion and metastasis of LSCC. Mechanically, we found the N6-methyladenosine (m6A) demethylase ALKBH5 mediates KCNQ1OT1 expression via an m6A-YTHDF2-dependent manner and KCNQ1OT1 could directly bind to HOXA9 to further regulate the proliferation, invasion and metastasis of LSCC cells. In general, our research indicates that ALKBH5-mediated m6A modification of KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9. CI - (c) 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Li, Yushan AU - Li Y AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Yan, Bingrui AU - Yan B AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Wang, Xin AU - Wang X AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Li, Qiuying AU - Li Q AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Kan, Xuan AU - Kan X AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Wang, Jingting AU - Wang J AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Sun, Yanan AU - Sun Y AUID- ORCID: 0000-0003-4587-3297 AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Wang, Peng AU - Wang P AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Tian, Linli AU - Tian L AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Liu, Ming AU - Liu M AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211201 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (RNA, Long Noncoding) RN - EC 1.14.11.- (ALKBH5 protein, human) RN - EC 1.14.11.- (AlkB Homolog 5, RNA Demethylase) SB - IM MH - AlkB Homolog 5, RNA Demethylase/genetics/metabolism MH - *Head and Neck Neoplasms MH - Humans MH - *RNA, Long Noncoding/genetics MH - Squamous Cell Carcinoma of Head and Neck MH - Up-Regulation/genetics PMC - PMC8743647 OTO - NOTNLM OT - ALKBH5 OT - HOXA9 OT - laryngeal squamous cell cancer OT - lncRNA KCNQ1OT1 OT - m6A methylation COIS- The authors declare that they have no competing interests. EDAT- 2021/12/02 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/01/01 CRDT- 2021/12/01 07:49 PHST- 2021/10/29 00:00 [revised] PHST- 2021/07/13 00:00 [received] PHST- 2021/11/11 00:00 [accepted] PHST- 2021/12/02 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/12/01 07:49 [entrez] PHST- 2022/01/01 00:00 [pmc-release] AID - JCMM17091 [pii] AID - 10.1111/jcmm.17091 [doi] PST - ppublish SO - J Cell Mol Med. 2022 Jan;26(2):385-398. doi: 10.1111/jcmm.17091. Epub 2021 Dec 1.