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A novel SOCS5/miR‐18/miR‐25 axis promotes tumorigenesis in liver cancer
Author(s) -
SanchezMejias Avencia,
Kwon Junsu,
Chew Xiao Hong,
Siemens Angela,
Sohn Hye Seon,
Jing Guo,
Zhang Bin,
Yang Henry,
Tay Yvonne
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31857
Subject(s) - carcinogenesis , downregulation and upregulation , microrna , liver cancer , cancer research , socs5 , cancer , biology , suppressor , medicine , hepatocellular carcinoma , gene , genetics , socs3
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.