N-methyladenosine-dependent Pri-miR-17-92 Maturation Suppresses PTEN/TMEM127 and Promotes Sensitivity to Everolimus in Gastric Cancer

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Oct 10

PMID 33037176

Citations 44

Authors

Yiting Sun

Song Li

Wenbin Yu

Zeyi Zhao

Jing Gao

Cheng Chen

Meng Wei

Teng Liu

Lanbo Li

Lian Liu

Affiliations

Soon will be listed here.

Abstract

N-methyladenosine (mA) is the most common epigenetic RNA modification with essential roles in cancer progression. However, roles of mA and its regulator METTL3 on non-coding RNA in gastric cancer are unknown. In this study, we found elevated levels of mA and METTL3 in gastric cancer. Increased METTL3 expression indicated poor outcomes of patients and high malignancy in vitro and in vivo. Mechanically, mA facilitated processing of pri-miR-17-92 into the miR-17-92 cluster through an mA/DGCR8-dependent mechanism. The mA modification that mediated this process occurred on the A879 locus of pri-miR-17-92. The miR-17-92 cluster activated the AKT/mTOR pathway by targeting PTEN or TMEM127. Compared with those with low levels of METTL3, METTL3-high tumors showed preferred sensitivity to an mTOR inhibitor, everolimus. These results reveal a perspective on epigenetic regulations of non-coding RNA in gastric cancer progression and provide a theoretical rationale for use of everolimus in the treatment of mA/METTL3-high gastric cancer.

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