Li FY, Fan TY, Zhang H, Sun YM. Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells. World J Gastroenterol 2021; 27(6): 470-486 [PMID: 33642822 DOI: 10.3748/wjg.v27.i6.470]
Corresponding Author of This Article
Ting-Yong Fan, MD, Chief Physician, Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, No. 440 Jiyan Road, Jinan 250117, Shandong Province, China. fantcwq50216@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Feb 14, 2021; 27(6): 470-486 Published online Feb 14, 2021. doi: 10.3748/wjg.v27.i6.470
Demethylation of miR-34a upregulates expression of membrane palmitoylated proteins and promotes the apoptosis of liver cancer cells
Fu-Yong Li, Ting-Yong Fan, Hao Zhang, Yu-Min Sun
Fu-Yong Li, Department of Interventional Radiology, Jinan City People's Hospital, Jinan 271100, Shandong Province, China
Ting-Yong Fan, Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan 250117, Shandong Province, China
Hao Zhang, Department of Endoscopy, Shandong Cancer Hospital affiliated to Shandong University, Jinan 250117, Shandong Province, China
Yu-Min Sun, Department of Cardiology, Jinan City People's Hospital, Jinan 271100, Shandong Province, China
Author contributions: Li FY conceived the idea; Fan TY conducted the analyses; Zhang H and Sun YM provided the data; All authors contributed to the writing and revisions.
Institutional review board statement: The study was reviewed and approved by the Shandong Cancer Hospital affiliated to Shandong University.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ting-Yong Fan, MD, Chief Physician, Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, No. 440 Jiyan Road, Jinan 250117, Shandong Province, China. fantcwq50216@163.com
Received: October 20, 2020 Peer-review started: October 20, 2020 First decision: December 8, 2020 Revised: December 21, 2020 Accepted: December 29, 2020 Article in press: December 29, 2020 Published online: February 14, 2021
ARTICLE HIGHLIGHTS
Research background
Liver cancer is the sixth most common cancer in the world. Although miR-34a and palmitoyl membrane protein (MPP2) are reportedly involved in various cell processes, their precise roles in liver cancer are unknown.
Research motivation
miR-34a expression is low in liver cancer. The promoter region of miR-34a has CpG-binding sites and miR-34a is hypermethylated in liver cancer. MPP2 was downstream of miR-34a via miRDB and TargetScan databases prediction.
Research objectives
This study investigated the expression of miR-34a, the methylation of miR-34a promoter, and the expression of MPP2 in liver cancer cells and their related mechanisms.
Research methods
The methylation degree of miR-34a promoter and the expression levels of miR-34a and MPP2 in the above samples were detected. miR-34a was demethylated by 5’-Za. miR-34a or MPP2 was upregulated by miR-34a mimics or MPP2 shRNA. The changes in proliferation, invasion, apoptosis, migration and other biological functions of liver cancer cells were observed. Double luciferase reporter genes were used to detect the targeting relationship between miR-34a and MPP2.
Research results
miR-34a and MPP2 were downregulated in liver cancer and miR-34a was highly methylated in liver cancer. After miR-34a demethylation/mimetic transfection/MPP2 overexpression, liver cancer cells apoptosis was increased, but the proliferation, invasion and migration capabilities were decreased. MPP2 was targeted by miR-34a.
Research conclusions
miR-34a demethylation upregulates the expression of MPP2 in liver cancer cells and promotes the apoptosis of liver cancer cells.
Research perspectives
The demethylation of miR-34a is a potential method for liver cancer treatment.
