Open AccessALKBH5‐mediated m6A modification of lncRNA KCNQ1OT1 triggers the development of LSCC via upregulation of HOXA9
Author(s) -
Li Yushan,
Yan Bingrui,
Wang Xin,
Li Qiuying,
Kan Xuan,
Wang Jingting,
Sun Yanan,
Wang Peng,
Tian Linli,
Liu Ming
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17091
Subject(s) - gene knockdown , downregulation and upregulation , demethylase , biology , cancer research , n6 methyladenosine , microarray analysis techniques , microbiology and biotechnology , gene expression , cell culture , gene , methylation , histone , genetics , methyltransferase
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.