N6-Methyladenosine Modification of PTTG3P Contributes to Colorectal Cancer Proliferation via YAP1

Frontiers in Oncology

Longfei Xie¹  Yue Wang¹  Yang Zheng²  Yiyang Liu³  Guohua Zhao⁴  Guilin Yu⁵  Jinnian Ge⁶ 

[1] Institute, Liaoning, China;;Department of Clinical Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital &;Department of General Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital &Department of General Surgery, The Central Hospital of Shenyang Medical College, Liaoning, China;Department of Physics and Integrative Biology, University of California, Berkeley, Berkeley, CA, United States;Department of Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China;

关键词: proliferation;    CRC;    METTL3;    IGF2BP2;    YAP1;   

DOI  :  10.3389/fonc.2021.669731

来源: DOAJ

【 摘 要 】

BackgroundLong noncoding RNAs (lncRNAs) have emerged to have irreplaceable roles in the epigenetic regulation of cancer progression, but their biological functions in colorectal cancer (CRC) remain unclear.MethodsLncRNA expression profiles in CRC tissue and their normal counterpart were explored. Through gain and loss of function approaches, the role of lncRNA PTTG3P was validated in relevant CRC cells and subcutaneous tumor model. The correlations of PTTG3P expression with clinical outcomes were assessed.ResultsPTTG3P was upregulated in CRC tissues and was closely correlated with unsatisfactory prognosis. PTTG3P facilitated glycolysis and proliferation, and the transcriptional regulator YAP1 was necessary for PTTG3P-induced proliferation. Mechanistically, the N6-methyladenosine (m6A) subunit METTL3 increased PTTG3P expression by influencing its stability, while insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could identify PTTG3P m6A methylation status and bind to it. IGF2BP2 knockdown partly recovered PTTG3P expression induced by METTL3, indicating that METTL3-regulated PTTG3P expression depended on the presence of IGF2BP2. Finally, rescue assays validated the critical role of the METTL3/PTTG3P/YAP1 axis on CRC proliferation.ConclusionsPTTG3P is an independent prognostic biomarker for CRC. The METTL3/PTTG3P/YAP1 axis promotes the progression of CRC and is a promising treatment target.

【 授权许可】

Unknown