m 6 A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2 ‐mediated IGF1R mRNA stabilization

作者：Chuandong Lang, Chi Yin, Kai‐Yuan Lin, Yue Li, Qing Yang, Zhengquan Wu, Hong Du, Dong Ren, Yuhu Dai, Xinsheng Peng · 发表于：Clinical and Translational Medicine · 年份：2021 · DOI：10.1002/ctm2.426 · 被引用次数：161 · 研究领域：RNA modifications and cancer、Cancer-related molecular mechanisms research、Cancer-related gene regulation

Abstract Background Bone metastasis is the leading cause of tumor‐related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved in the progression of multiple cancers. Nevertheless, the role of lncRNAs in PCa bone metastasis remains largely unclear. Methods The expression of prostate cancer‐associated transcripts was analyzed in published datasets and further verified in clinical samples and cell lines by RT‐qPCR and in situ hybridization assays. Colony formation assay, MTT assay, cell cycle analysis, EdU assay, Transwell migration and invasion assays, wound healing assay, and in vivo experiments were carried out to investigate the function of prostate cancer‐associated transcript 6 ( PCAT6 ) in bone metastasis and tumor growth of PCa. Bioinformatic analysis, RNA pull‐down, and RIP assays were conducted to identify the proteins binding to PCAT6 and the potential targets of PCAT6 . The therapeutic potential of targeting PCAT6 by antisense oligonucleotides (ASO) was further explored in vivo . Results PCAT6 was upregulated in PCa tissues with bone metastasis and increased PCAT6 expression predicted poor prognosis in PCa patients. Functional experiments found that PCAT6 knockdown significantly inhibited PCa cell invasion, migration, and proliferation in vitro , as well as bone metastasis and tumor growth in vivo . Mechanistically, METTL3 ‐mediated m 6 A modification contributed to PCAT6 upregulation in an IGF2BP2 ‐dependen...