miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway

Sijie Xie; Xiaoxue Jiang; Rushi Qin; Shuting Song; Yanan Lu; Liyan Wang; Yingjie Chen; Dongdong Lu

doi:10.1016/j.isci.2021.103271

miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway

iScience. 2021 Oct 14;24(11):103271. doi: 10.1016/j.isci.2021.103271. eCollection 2021 Nov 19.

Authors

Sijie Xie¹, Xiaoxue Jiang¹, Rushi Qin¹, Shuting Song¹, Yanan Lu¹, Liyan Wang¹, Yingjie Chen¹, Dongdong Lu¹

Affiliation

¹ Shanghai Putuo People's Hospital, School of Life Science and Technology, Tongji University, 200092 Shanghai, China.

Abstract

miR-1307 is highly expressed in liver cancer and inhibits methyltransferase protein8. Thereby, miR-1307 inhibits the expression of KDM3A and KDM3B and increases the methylation modification of histone H3 lysine 9, which enhances the expression of endoplasmic-reticulum-related gene CALR. Of note, miR-1307 weakens the binding ability of OSTC to CDK2, CDK4, CyclinD1, and cyclinE and enhances the binding ability of CALR to CDK2, CDK4, CyclinD1, and cyclinE, decreasing of p21WAF1/CIP1, GADD45, pRB, and p18, and decreasing of ppRB. Furthermore, miR-1307 increases the activity of H-Ras, PKM2, and PLK1. Strikingly, miR-1307 reduces the binding ability of OSTC to ATG4 and enhances the binding ability of CALR to ATG4. Therefore, miR-1307 reduces the occurrence of autophagy based on ATG4-LC3-ATG3-ATG7-ATG5-ATG16L1-ATG12-ATG9- Beclin1. In particular, miR-1307 enhances the expression of PAK2, PLK1, PRKAR2A, MYBL1, and Trim44 and inhibits the expression of Sash1 and Smad5 via autophagy. Our observations suggest that miR-1307 promotes hepatocarcinogenesis by CALR-OSTC-endoplasmic reticulum protein folding pathway.

Keywords: Cancer; Cell biology; Molecular biology.