COMMD10 Inhibited DNA Damage to Promote the Progression of Gastric Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Jun 13

PMID 38871970

Authors

Xiaohua Liu

Xiaocheng Mao

Chao Zhu

Hongfei Liu

Yangyang Fang

Tianmei Fu

Linwei Fan

Mengwei Liu

Ziqing Xiong

Hong Tang

Piaoping Hu

Aiping Le

Affiliations

Soon will be listed here.

Abstract

Purpose: The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC).

Methods: Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage.

Results: The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM-p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM-p53 signaling pathway in xenograft tumor tissue.

Conclusion: COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.

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