MKRN2 promotes gastric cancer progression by suppressing autophagy via the PI3K/Akt/mTOR signaling pathway.

Authors

Miao Wang, Nan Hou, Honglei Wang, Xuqing Ding, Xinchao Sun, Junjie Tu

Published in

American journal of cancer research. Volume 16. Issue 9. Pages 4152-4169. Epub Sep 25, 2026.

Abstract

Makorin ring finger protein 2 (MKRN2) is associated with the development of various tumors; however, few studies have investigated the role MKRN2 in gastric cancer (GC). This study aimed to investigate the expression and underlying mechanism of MKRN2 in GC. Quantitative real-time PCR (qRT-PCR) and western blotting were adopted to detect MKRN2 expression in GC cells. Cell viability, colony formation, and apoptosis were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Cell invasion and migration were evaluated using transwell and scratch healing assays. Flow cytometry and immunofluorescence were performed to evaluate M1/M2 macrophage phenotypes. Western blotting was adopted to measure the expression of autophagy-related proteins and components of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. An in vivo xenograft mouse model was established by subcutaneous injection of MKN-45 cells. The expression Ki-67 and MKRN2 in GC tissues was detected by immunohistochemistry (IHC). MKRN2 expression was elevated in GC. MKRN2 overexpression promoted cell proliferation, migration and invasion, whereas MKRN2 knockdown inhibited those cellular behaviors. MKRN2 knockdown increased LC3-II/LC3-I ratio and Beclin1 expression, and decreased p62 level, whereas MKRN2 overexpression produced the opposite effects. Treatment with 3-methyladenine (3-MA) partly reversed autophagy-related changes in GC cells induced by MKRN2 knockdown. On contrary, rapamycin (RAPA) treatment counteracted the inhibition of autophagy caused by MKRN2 overexpression. MKRN2 knockdown reduced xenograft tumor growth in mice. Moreover, MKRN2 knockdown inhibited the phosphorylation and activation of the PI3K/Akt/mTOR pathway. MKRN2 knockdown inhibited M2 macrophage polarization and promoted M1 macrophage polarization. MKRN2 may partook in the pathogenesis and development of GC as an oncogene. These findings laid a foundation for the development of targeted therapy in GC progression.

PMID:
42908866
Bibliographic data and abstract were imported from PubMed on 23 Oct 2026.

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