MicroRNA-328-3p facilitates the progression of gastric cancer via KEAP1/NRF2 axis

• Published in: Free radical research Vol. 55; no. 6; pp. 595 - 605
• Main Authors: Xiao, Zhe, Zheng, Yong-Bin, Dao, Wen-Xin, Luo, Jian-Fei, Deng, Wen-Hong, Yan, Rui-Cheng, Liu, Jia-Sheng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.06.2021
• Subjects: apoptosis; Disease Progression; gastric cancer; Humans; Kelch-Like ECH-Associated Protein 1 - metabolism; MicroRNAs - metabolism; miR-328-3p; NF-E2-Related Factor 2 - metabolism; NRF2; oxidative stress; Signal Transduction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; apoptosis; miR-328-3p; NRF2; gastric cancer; oxidative stress
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715762.2021.1923705

Gastric cancer is a common lethal malignancy and causes great cancer-related mortality worldwide. MicroRNA (miR)-328-3p is implicated in the progression of various human cancers; however, its role and mechanism in the progression of gastric cancer remain unclear.Human gastric cancer cells were incubated with miR-328-3p mimic, inhibitor or the matched negative control. Cell viability, colony formation, migrative and invasive capacity, cell apoptosis and oxidative stress were measured. To clarify the involvement of nuclear factor-E2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1), small interfering RNA was used. miR-328-3p was upregulated in human gastric cancer cells and tissues, and its level positively correlated with the progression of gastric cancer. miR-328-3p promoted cell viability, colony formation, migration and invasion, thereby facilitating the progression of gastric cancer. miR-328-3p mimic reduced, while miR-328-3p inhibitor increased apoptosis and oxidative stress of human gastric cancer cells. Mechanistically, miR-328-3p upregulated NRF2 via targeting KEAP1to attenuate excessive free radical production and cell apoptosis. miR-328-3p functions as an oncogenic gene and inhibiting miR-328-3p may help to develop novel therapeutic strategies of human gastric cancer.