miR-373 Suppresses Cell Proliferation and Apoptosis via Regulation of SIRT1/PGC-1α/NRF2 Axis in Pancreatic Cancer

(Pages: 199-210)
Qing-Hua Yin, M.D, 1Yuan Zhou, M.D, 1Zhi-Yuan Li, M.D, 2,*
Department of Hepatobiliary Surgery, The First Hospital of Changsha, Changsha 410000, P.R.China
Department of Gastrointestinal Surgery, The Central Hospital of Hengyang City, Hengyang 421001, P.R.China
Department of Hepatobiliary Surgery, The First Hospital of Changsha, Changsha 410000, P.R.China
Department of Gastrointestinal Surgery, The Central Hospital of Hengyang City, Hengyang 421001, P.R.China
*Corresponding Address: Department of Gastrointestinal Surgery The Central Hospital of Hengyang City Hengyang 421001 P.R.China Email:183081297@qq.com
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Yin Qing-Hua, Zhou Yuan, Li Zhi-Yuan. miR-373 Suppresses Cell Proliferation and Apoptosis via Regulation of SIRT1/PGC-1α/NRF2 Axis in Pancreatic Cancer. Cell J. 2021; 23(2): 199-210.

Abstract

Objective

Our study aimed to investigate function and mechanism of miR-373 in proliferation and apoptosis of pancreatic cancer (PC) cells by regulating NAD+-dependent histone deacetylase sirtulin 1 (SIRT1).

Materials and Methods

This experimental study included two PC cell lines AsPC-1 and PANC-1 in which expression levels of miR-373 and SIRT1 were manipulated. The level of miR-373 was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Expression levels of SIRT1, BCL-2, BAX, cleaved CASPASE-8/9/3, PARP, PGC-1α, NRF2, eNOS and iNOS were examined via RT-qPCR and western blotting, respectively. The binding sites of miR-373 on the SIRT1 were examined via dual-luciferase assay. Cell proliferation and apoptosis were examined by MTT assay, colony formation assay, Annexin-V/PI staining and TUNEL assay. The oxidative metabolic changes were monitored by reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) detection.

Results

miR-373 could specifically target the 3’-UTR of SIRT1 and reduce its expression in PC cells. Either elevated expression of miR-373 or partial loss of SIRT1 inhibited cell proliferation and induced cell apoptosis. Accumulation of BAX and cleaved CASPASE-8/9/3, inhibition of PGC-1α/NRF2 pathway, increase oxidative stress and reduction of BCL-2 as well as uncleaved PARP were found in the presence of miR-373 or the absence of SIRT1. Overexpression of SIRT1 could reduce anti-proliferative and pro-apoptotic effects of miR-373.

Conclusion

Overall, this study concluded that miR-373-dependent SIRT1 inhibition displays anti-proliferative and pro- apoptotic roles in PC cells via PGC-1α/NRF2 pathway, which highlights miR-373 as a potential target for PC treatment.