Silencing PSME3 induces colorectal cancer radiosensitivity by downregulating the expression of cyclin B1 and CKD1

Author:

Song Wen123,Guo Cuiping4,Chen Jianxiong12,Duan Shiyu12,Hu Yukun12,Zou Ying5,Chi Honggang5,Geng Jian12,Zhou Jun12ORCID

Affiliation:

1. Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

2. Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China

3. Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

4. Department of Emergency, Zhumadian Second Hospital of Traditional Chinese Medicine, Zhumadian 463000, China

5. Department of Traditional Chinese Medicine, Scientific Research Platform, The Second School of Clinical Medicine, Guangdong Medical University, Dongguan 523808, China

Abstract

Resistance to radiotherapy remains a severe obstacle in the treatment of high-risk colorectal cancer patients. Recent studies have indicated that proteasome activator complex subunit 3 (PSME3) participates in the development and progression of various human malignancies and is proposed to play a role in tumor radioresistance. However, the impact of PSME3 on radioresistance of colorectal cancer has been largely unknown. In the present study, the enhanced expression of PSME3 was observed in colorectal cancer cells and tissue. Upregulation of PSME3 was significantly implicated in lymph node state, lymphovascular invasion, and Dukes' stage. Furthermore, high PSME3 expression was closely linked to poorer overall and progression-free survival in patients with colorectal cancer. The study further demonstrated that the proliferative, invasive and migratory potential of colorectal cancer cells was effectively inhibited in vitro after silencing PSME3. Our results verified that knockdown of PSME3 probably triggered cell cycle arrest at the G2/M phase by downregulation of cyclinB1 and CDK1, thereby enhancing the radiosensitivity of colorectal cancer cells. These data illustrated that PSME3 is a promising biomarker predictive of colorectal cancer prognosis and silencing of PSME3 may provide with a new approach for sensitizing the radiotherapy in colorectal cancer. Impact statement It is reported that colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer-related death. At present, the main treatment method of colorectal cancer is surgery, supplemented by radiotherapy and chemotherapy. Among them, radiotherapy plays an important role in the treatment of locally advanced colorectal cancer, surgery, and chemotherapy. Our study found that down-regulation of PSME3 may enhance the radiosensitivity of CRC cells by triggering cell cycle arrest, which suggests that silence PSME3 may provide a new method for improving the radiosensitivity of CRC. What’more, our research also demonstrated that PSME3 may promote proliferation, invasive and migratory potential of CRC cells, which implies that PSME3 might be a biomarker of CRC for early diagnosis and treatment.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

"Group-type" Special Support Project for Education Talents in Universities

Publisher

SAGE Publications

Subject

General Biochemistry, Genetics and Molecular Biology

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