m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma

作者：Li Liu, Jing Wang, Guifeng Sun, Qiong Wu, Ji Ma, Xin Zhang, Nan Huang, Zhixuan Bian, Song Gu, Min Xu, Minzhi Yin, Fenyong Sun, Qiuhui Pan · 发表于：Molecular Cancer · 年份：2019 · DOI：10.1186/s12943-019-1119-7 · 被引用次数：211 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、HVDC Systems and Fault Protection

Abstract Background N 6 -Methyladenosine (m 6 A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m 6 A modification in hepatoblastoma (HB). Methods We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m 6 A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m 6 A-Seq was used to profiled m 6 A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB. Results In this research, we discovered that m 6 A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m 6 A modification. We also profiled m 6 A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m 6 A is highly expressed in hepatoblastoma tumors. Also, m 6 A is enriched not only around the stop codon, ...