M6A-mediated up-regulation of LncRNA LIFR-AS1 enhances the progression of pancreatic cancer via miRNA-150-5p/ VEGFA/Akt signaling. Issue 23 (2nd December 2021)

• Record Type: Journal Article
• Authors: Chen, Jian-Qing; Tao, Yuan-Ping; Hong, Yong-Gang; Li, Hui-Fen; Huang, Zhi-Ping; Xu, Xuan-Fu; Zheng, Hao; Hu, Liang-Kai
• Is Part Of: Cell cycle. Volume 20:Issue 23(2021)
• Page Start: 2507
• Page End: 2518
• Publication Date: 2021-12-02
• Subjects: LIFR-AS1 -- pancreatic cancer -- m6A -- VEGFA -- PI3K/Akt signaling; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2021.1991122
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: N 6 -methyladenosine (m 6 A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. There is extensive evidence indicating that long non-coding RNAs (lncRNAs) serve as key regulators of oncogenesis and tumor progression in humans. Through prior study has assessed that LIFR-AS1 plays a key role in various kinds of malignant tumors. However, the exact role of m 6 A induced LIFR-AS1 in pancreatic cancer (PC) and its potential molecular mechanisms remain largely unknown. In this study, we determined that PC cell lines and tumors exhibit increased LIFR-AS1 expression that correlates with larger tumor size, lymph node metastasis, and more advanced TNM stage. Functionally, loss-of-function studies indicated that LIFR-AS1 knockdown decreased the proliferation, migration, and invasion of PC cells in vitro. Mechanistically, we found that METTL3 induced m 6 A hyper-methylation on the 3′ UTR of LIFR-AS1 to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. Through rescue experiments, we were able to confirm that the unfavorable impact of LIFR-AS1 knockdown on VEGFA /PI3K/Akt Signaling could be reversed via the inhibition of miR-150-5p expression. Together, these findings indicate that a noval m6A-LIFR-AS1 axis promotes PC progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis may be a viable clinical target for the treatment of PC.