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

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.

CircMEG3 inhibits telomerase activity by reducing Cbf5 in human liver cancer stem cells.

Circular RNA (CircRNA) is a newly identified special class of non-coding RNA (ncRNA) that plays an important regulatory role in the progression of certain diseases. Herein, our results indicate that CircMEG3 is downregulated expression and negatively correlated with the expression of telomerase-related gene Cbf5 in human liver cancer. Moreover, CircMEG3 inhibits the growth of human liver cancer stem cells in vivo and in vitro. CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of Cbf5, a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. Thereby, CircMEG3 inhibits telomerase activity and shortens telomere lifespan dependent on HULC and Cbf5 in human liver cancer stem cell. Strikingly, increased Cbf5 abrogates the ability of CircMEG3 to inhibit malignant differentiation of human liver cancer stem cells. In summary, these observations provide important basic information for finding effective liver cancer therapeutic targets.