lncRNA ZNRD1-AS1 promotes malignant lung cell proliferation, migration, and angiogenesis via the miR-942/TNS1 axis and is positively regulated by the m6A reader YTHDC2

作者：Jin Wang, Lirong Tan, Xueting Yu, Xiyuan Cao, Beibei Jia, Rui Chen, Jianxiang Li · 发表于：Molecular Cancer · 年份：2022 · DOI：10.1186/s12943-022-01705-7 · 被引用次数：112 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、interferon and immune responses

Abstract Rationale Lung cancer is the most prevalent form of cancer and has a high mortality rate, making it a global public health concern. The N 6 -methyladenosine (m 6 A) modification is a highly dynamic and reversible process that is involved in a variety of essential biological processes. Using in vitro, in vivo, and multi-omics bioinformatics, the present study aims to determine the function and regulatory mechanisms of the long non-coding (lnc)RNA zinc ribbon domain-containing 1-antisense 1 (ZNRD1-AS1). Methods The RNAs that were bound to the m 6 A ‘reader’ were identified using YTH domain-containing 2 (YTHDC2) RNA immunoprecipitation (RIP)-sequencing. Utilizing methylated RIP PCR/quantitative PCR, pull-down, and RNA stability assays, m 6 A modification and ZNRD1-AS1 regulation were analyzed. Using bioinformatics, the expression levels and clinical significance of ZNRD1-AS1 in lung cancer were evaluated. Using fluorescent in situ hybridization and quantitative PCR assays, the subcellular location of ZNRD1-AS1 was determined. Using cell migration, proliferation, and angiogenesis assays, the biological function of ZNRD1-AS1 in lung cancer was determined. In addition, the tumor suppressor effect of ZNRD1-AS1 in vivo was validated using a xenograft animal model. Through bioinformatics analysis and in vitro assays, the downstream microRNAs (miRs) and competing endogenous RNAs were also predicted and validated. Results This study provided evidence that m 6 A modification med...