A novel SOCS5/miR-18/miR-25 axis promotes tumorigenesis in liver cancer.

Abstract

The role of miRNAs with tumor suppressive activity in liver cancer has been well studied. However, little is known about potential oncomiRs in HCC. In our study, we conducted a systematic evaluation of candidate oncomiRs and found that upregulation of miR-18a and miR-25 in HCC was associated with poor patient survival and promoted proliferation in HCC cell lines. These two miRNAs belong to the polycistronic paralogous miR-17-92 and miR-25-106b clusters respectively. Although the members of both clusters are often upregulated in HCC, the contribution of individual miRNAs in these clusters to HCC tumorigenesis is not fully understood. We validated SOCS5 as a bona fide target of both miRNAs, and established, for the first time, the tumor suppressive role of SOCS5 in liver cancer. We further investigated the mechanism by which SOCS5 contributes to tumorigenesis, demonstrated that this SOCS5/miR-18a/miR-25 axis regulates the tumor suppressor TSC1 and downstream mTOR signaling, and highlighted the potential therapeutic use of miR-18a and miR-25 inhibition in restoring SOCS5 levels in HCC.

• Authors: Avencia Sanchez-Mejias, Junsu Kwon, Xiao Hong Chew, Angela Siemens, Hye Seon Sohn, Guo Jing, Bin Zhang, Henry Yang, Yvonne Tay
• Journal: International journal of cancer (Int J Cancer) Vol. 144 Issue 2 Pg. 311-321 (01 15 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30191950 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 UICC.

Chemical References

• MIRN18 microRNA, human
• MIRN25 microRNA, human
• MicroRNAs
• SOCS5 protein, human
• Suppressor of Cytokine Signaling Proteins

Topics

• Carcinogenesis (genetics)
• Carcinoma, Hepatocellular (genetics, pathology)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Liver Neoplasms (genetics, pathology)
• MicroRNAs (genetics)
• Suppressor of Cytokine Signaling Proteins (biosynthesis, genetics)