PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway

被引：21

作者：

Liu, Tao ^{[1
]}

Zhang, Junling ^{[2
]}

Chen, Hu ^{[3
]}

Bianba, Tashi ^{[3
]}

Pan, Yisheng ^{[2
]}

Wang, Xin ^{[2
]}

Jiang, Yong ^{[2
]}

Yang, Zhen ^{[1
]}

机构：

[1] Zhengzhou Univ, Affiliated Hosp 1, Gastrointestinal Surg, Zhengzhou, Peoples R China

[2] Peking Univ First Hosp, Dept Gen Surg, 8 XiShiKu St, Beijing, Peoples R China

[3] Tibet Autonomous Reg Peoples Hosp, Dept Gen Surg, 18 Linkor North Roud, Lasha, Tibet Autonomou, Peoples R China

来源：

ONCOGENESIS | 2022年 / 11卷 / 01期

关键词：

CELL-PROLIFERATION; PANCREATIC-CANCER; PROTEIN; EXPRESSION;

D O I：

10.1038/s41389-022-00386-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

As one of the most common malignant tumors, it is particularly important to further understand the development mechanism of gastric cancer and to find more effective therapeutic target genes. The results of immunohistochemical staining showed that PSMC2 was upregulated in gastric cancer. Cell function experiments indicated that PSMC2 knockdown inhibited the proliferation, done formation and migration of gastric cancer cells, and induced apoptosis. In vivo experiments further showed that PSMC2 knockdown suppressed tumor growth. RPS15A and mTOR pathway were identified the downstream gene and pathway of PSMC2 by GeneChip and IPA. PSMC2 knockdown inhibited RPS15A expression and mTOR pathway, which was neutralized by RPS15A overexpression. Overexpression of RPS15A promoted the proliferation and migration of gastric cancer cells, which alleviated the inhibitory effect caused by PSMC2 knockdown to a certain extent. The mTOR pathway inhibitor Torin1 partially restored the promoting role of RPS15A overexpression on the gastric cancer cell proliferation. Furthermore, bioinformatics analysis and dual-luciferase reporter assays showed that PSMC2 and RPS15A competitively bound to hsa-let-7c-3p. Inhibition of hsa-let-7c-3p promoted the migration of MGC-803 cells and reduced the apoptosis level, while simultaneous inhibition PSMC2 and hsa-let-7c-3p restored the migration and apoptosis levels of gastric cancer cells. In conclusion, PSMC2 and RPS15A were highly expressed in gastric cancer. PSMC2 enhanced RPS15A levels by targeting hsa-let-7c-3p, and then activated mTOR pathway, thereby promoting the progression of gastric cancer. [GRAPHICS] .

引用

页数：12

共 34 条

[1] Microdissecting the role of microRNAs in the pathogenesis of prostate cancer [J].

Ayub, Shiekh Gazalla ;

Kaul, Deepak ;

Ayub, Taha .

CANCER GENETICS, 2015, 208 (06) :289-302

[2] Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome [J].

Dong, Yuanchen ;

Zhang, Shuwen ;

Wu, Zhaolong ;

Li, Xuemei ;

Wang, Wei Li ;

Zhu, Yanan ;

Stoilova-McPhie, Svetla ;

Lu, Ying ;

Finley, Daniel ;

Mao, Youdong .

NATURE, 2019, 565 (7737) :49-+

[3] Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome [J].

Finley, Daniel .

ANNUAL REVIEW OF BIOCHEMISTRY, 2009, 78 :477-513

[4] Exosomes in gastric cancer: roles, mechanisms, and applications [J].

Fu, Min ;

Gu, Jianmei ;

Jiang, Pengcheng ;

Qian, Hui ;

Xu, Wenrong ;

Zhang, Xu .

MOLECULAR CANCER, 2019, 18

[5] The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target [J].

Gambardella, V ;

Castillo, J. ;

Tarazona, N. ;

Gimeno-Valiente, F. ;

Martinez-Ciarpaglini, C. ;

Cabeza-Segura, M. ;

Rosello, S. ;

Roda, D. ;

Huerta, M. ;

Cervantes, A. ;

Fleitas, T. .

CANCER TREATMENT REVIEWS, 2020, 86

[6] Functional SNP in 3-UTR MicroRNA-Binding Site of ZNF350 Confers Risk for Age-Related Cataract [J].

Gu, Shanshan ;

Rong, Han ;

Zhang, Guowei ;

Kang, Lihua ;

Yang, Mei ;

Guan, Huaijin .

HUMAN MUTATION, 2016, 37 (11) :1223-1230

[7] Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis [J].

Guan, Yibing ;

Xu, Fangshi ;

Wang, Yiyuan ;

Tian, Juanhua ;

Wan, Ziyan ;

Wang, Zhenlong ;

Chong, Tie .

BMC MEDICAL GENOMICS, 2020, 13 (01) :140

[8] Ribosomal protein S15a promotes tumor angiogenesis via enhancing Wnt/β-catenin-induced FGF18 expression in hepatocellular carcinoma [J].

Guo, Pengyi ;

Wang, Yi ;

Dai, Chunxiu ;

Tao, Chonglin ;

Wu, Fang ;

Xie, Xiaozai ;

Yu, Haitao ;

Zhu, Qiandong ;

Li, Junjian ;

Ye, Longyun ;

Yu, Fuxiang ;

Shan, Yunfeng ;

Yu, Zhengping ;

Dhanasekaran, Renumathy ;

Zheng, Rongyuan ;

Chen, Gang .

ONCOGENE, 2018, 37 (09) :1220-1236

[9] Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration [J].

He, Jinghu ;

Xing, Junjie ;

Yang, Xiaohong ;

Zhang, Chenxin ;

Zhang, Yixiang ;

Wang, Hao ;

Xu, Xiaodong ;

Wang, Hantao ;

Cao, Yi ;

Xu, Haonan ;

Zhang, Chuansen ;

Wang, Chen ;

Yu, Enda .

CHEMOTHERAPY, 2019, 64 (03) :146-154

[10] Assembly Pathway of the Mammalian Proteasome Base Subcomplex Is Mediated by Multiple Specific Chaperones [J].

Kaneko, Takeumi ;

Hamazaki, Jun ;

Iemura, Shun-ichiro ;

Sasaki, Katsuhiro ;

Furuyama, Kaori ;

Natsume, Tohru ;

Tanaka, Keiji ;

Murata, Shigeo .

CELL, 2009, 137 (05) :914-925

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