Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a

Abstract

It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/β-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial-mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

“…FTX is also involved in liver cancer, but its role is more complicated. On the one hand, FTX can bind MCM2 and miR-374a to inhibit tumour cell proliferation [48]. On the other hand, FTX can produce miR-545, which promotes tumour cell proliferation [49].…”

Propofol Inhibits Proliferation, Migration, Invasion and Promotes Apoptosis Through Down-Regulating miR-374a in Hepatocarcinoma Cell Lines

“…Herein, the alteration of proteins related to Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry apoptosis after propofol treatments was consistent with the previous literature, supporting the pro-apoptotic role of propofol. miR-374a has been reported as an oncogene in diverse tumor types, including HCC [36,37]. In the literature by He et al, miR-374a could promote osteosarcoma cell proliferation through down-regulating FOXO1 expression [38].…”

Long non-coding RNA CCAT2 is associated with poor prognosis in hepatocellular carcinoma and promotes tumor metastasis by regulating Snail2-mediated epithelial–mesenchymal transition

“…Knockdown of lncRNA SPRY4-IT1 inhibited the migration and invasion of colorectal cancer cells and induced cell cycle arrest 19. The lncRNA FTX could inhibit HCC cell growth and metastasis both in vitro and in vivo 20. CCAT2 has also been shown to promote proliferation and invasion in breast,10 lung11 and cervical cancer cells 21.…”

“…To date, the detailed molecular mechanism through which CCAT2 contributes to HCC progression is still unclear. Recent studies have revealed that some lncRNAs can regulate tumor cell metastasis by affecting the EMT process in HCC 20,24,25. Therefore, we further analyzed the relationship between CCAT2 and EMT in HCC.…”