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MKRN2 通过下调 PKM2 抑制胃癌的增殖。

MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2.

机构信息

The Second Hospital of Lanzhou University, Lanzhou 730000, P.R. China.

School of Public Health, Lanzhou University, Lanzhou 730000, P.R. China.

出版信息

Aging (Albany NY). 2022 Feb 23;14(4):2004-2013. doi: 10.18632/aging.203643.

DOI:10.18632/aging.203643
PMID:35196650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8908937/
Abstract

Cumulative evidence suggests that dysfunction of ubiquitinating enzymes is responsible for multiple types of diseases including cancer. However, what role the ubiquitinating enzyme plays in gastric cancer remains unknown. In this study, using bioinformatics analysis and a series of experimental analyses, we found that an E3 ubiquitin-protein, MKRN2 was down-regulated in gastric cancer tissues. Kaplan-Meier survival analysis showed the low MKRN2 expression significantly indicated poor prognosis. Overexpression of MKRN2 notably inhibited cell proliferation and . Conversely, knockdown of MKRN2 had the opposite effects . Additionally, the mechanical analysis indicated that MKRN2 promoted ubiquitination-mediated degradation of PKM2 and attenuated its effect on ERK. Overall, the present study suggests that MKRN2 may be a potential therapeutic target for gastric cancer.

摘要

累积的证据表明，泛素化酶的功能障碍与包括癌症在内的多种疾病有关。然而，泛素化酶在胃癌中扮演何种角色尚不清楚。在这项研究中，我们通过生物信息学分析和一系列实验分析发现，E3 泛素蛋白 MKRN2 在胃癌组织中表达下调。Kaplan-Meier 生存分析表明，MKRN2 低表达显著提示预后不良。MKRN2 的过表达显著抑制了细胞的增殖和侵袭。相反，MKRN2 的敲低则产生相反的效果。此外，机制分析表明，MKRN2 促进了 PKM2 的泛素化介导降解，并减弱了其对 ERK 的作用。总体而言，本研究提示 MKRN2 可能是胃癌的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/c1210585d6ac/aging-14-203643-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/a0cb13b2f934/aging-14-203643-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/e6e85c1487ac/aging-14-203643-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/90f790835214/aging-14-203643-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/6d2b731311e4/aging-14-203643-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/76ded2a1ad09/aging-14-203643-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/c1210585d6ac/aging-14-203643-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/a0cb13b2f934/aging-14-203643-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/e6e85c1487ac/aging-14-203643-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/90f790835214/aging-14-203643-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/6d2b731311e4/aging-14-203643-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/76ded2a1ad09/aging-14-203643-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be8c/8908937/c1210585d6ac/aging-14-203643-g006.jpg

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