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Updated: Oct 2, 2025

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Published on: April 2, 2020
MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2
Zheng Liu1, Shuyao Xiang2, Xingchen Guo1
1The Second Hospital of Lanzhou University, Lanzhou 730000, P.R. China.
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 in vitro and in vivo. Conversely, knockdown of MKRN2 had the opposite effects in vitro. 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.
Insights
The E3 ubiquitin-protein MKRN2 is down-regulated in gastric cancer, inhibiting cell proliferation and indicating poor prognosis. MKRN2 may serve as a potential therapeutic target for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Dysfunction of ubiquitinating enzymes is linked to various diseases, including cancer.
- The specific role of ubiquitinating enzymes in gastric cancer pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role of the E3 ubiquitin-protein MKRN2 in gastric cancer.
- To determine if MKRN2 expression levels correlate with patient prognosis and tumor progression.
Main Methods:
- Bioinformatics analysis of gastric cancer tissues.
- Experimental validation including cell proliferation assays (in vitro and in vivo).
- Analysis of MKRN2's mechanism involving PKM2 ubiquitination and ERK signaling.
Main Results:
- MKRN2 was found to be significantly down-regulated in gastric cancer tissues.
- Low MKRN2 expression correlated with poor patient prognosis.
- Overexpression of MKRN2 inhibited gastric cancer cell proliferation, while knockdown promoted it.
- MKRN2 facilitates the ubiquitination-mediated degradation of PKM2, thereby attenuating its effect on ERK.
Conclusions:
- MKRN2 plays a suppressive role in gastric cancer progression.
- MKRN2 functions by promoting PKM2 degradation, impacting the ERK pathway.
- MKRN2 represents a potential therapeutic target for gastric cancer treatment.
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