J Cancer 2020; 11(17):5042-5055. doi:10.7150/jca.45553

Research Paper

The miR-370/UQCRC2 axis facilitates tumorigenesis by regulating epithelial-mesenchymal transition in Gastric Cancer

Dan-wen Wang1,2,5,6, Fei Su3, Tao Zhang3,4, Tie-cheng Yang1,2,6, Hua-qiao Wang1,2,6, Li-jie Yang1,2,6, Fen-fang Zhou1,2,5, Mao-hui Feng1,2,5,6,7✉

1. Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, People's Republic of China.
2. Center for Clinical Medicine of Peritoneal Cancer of Wuhan, Wuhan 430071, Hubei Province, People's Republic of China.
3. Department of Oncology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, People's Republic of China.
4. The Second Clinical Medical College of Lanzhou University, Lanzhou 730030, Gansu Province, People's Republic of China.
5. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.
6. Clinical Cancer Study Center of Hubei Province, Wuhan 430071, Hubei Province, People's Republic of China.
7. Key Laboratory of Tumor Biological Behavior of Hubei Province, Wuhan 430071, Hubei Province, People's Republic of China.

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Citation:
Wang Dw, Su F, Zhang T, Yang Tc, Wang Hq, Yang Lj, Zhou Ff, Feng Mh. The miR-370/UQCRC2 axis facilitates tumorigenesis by regulating epithelial-mesenchymal transition in Gastric Cancer. J Cancer 2020; 11(17):5042-5055. doi:10.7150/jca.45553. Available from https://www.jcancer.org/v11p5042.htm

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Abstract

Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) is an important mitochondrial complex III subunit. This study investigated the role of UQCRC2 in gastric cancer (GC) and its upstream regulatory microRNAs (miRNAs). UQCRC2 expression levels were lower in GC tissues than non-carcinoma tissues. Furthermore, UQCRC2 levels were negatively correlated with lymph node metastasis, relapse, and tumor grade. Bioinformatics analysis predicted UQCRC2 as the target gene for miR-370, and this was verified in luciferase reporter assays. MiR-370 levels were inversely correlated with UQCRC2 levels in GC. UQCRC2 overexpression suppressed GC cell migration and invasion in vitro and in vivo, whereas up-regulating miR-370 reversed these effects. Western blotting analysis showed that miR-370 targeted UQCRC2 and positively regulated the epithelial-mesenchymal transition (EMT) signaling pathway in GC cells. Therefore, the miR-370/UQCRC2 axis may regulate EMT signaling pathways to affect tumor proliferation and metastasis and is, thus, a potential target for GC treatment.

Keywords: microRNA-370, UQCRC2, gastric cancer, tumor metastasis, epithelial-mesenchymal transition, proliferation