title: Identification a novel tumor-suppressive hsa-miR-599 regulates cells proliferation, migration and invasion by targeting oncogenic MYC in hepatocellular carcinoma.
abstract: Increasing evidences have demonstrated that microRNAs (miRNAs) act an essential role in regulating tumor progression and metastasis. Previous miRNAs microarray data showed that hsa-miR-599 is lower expressed in hepatocellular carcinoma (HCC); however, the function and molecular mechanism of hsa-miR-599 on HCC has not been well illustrated. Here, we first analyzed the expression level of hsa-miR-599 in HCC tissues and cell lines by real-time reverse-transcription PCR (qRT-PCR). Interestingly, we found that hsa-miR-599 was significantly down-regulated in the examined HCC tissues and cell lines. Then cells proliferation, migration and invasion were assessed by MTT, wound-healing and trans-well assay respectively. The results showed that over-expression of hsa-miR-599 resulted in inhibited HCC cells proliferation, migration and invasion in vitro. In addition, dual-luciferase reporter assay, qRT-PCR and Western blot analyzes were used to confirm MYC (v-myc avian myelocytomatosis viral oncogene homolog) as a target gene of hsa-miR-599. MYC expression was up-regulated in HCC tissues and cell lines, and restoration of hsa-miR-599 could remarkably decreased the mRNA and protein levels of MYC. Moreover, over-expression of MYC partly reversed hsa-miR-599-mediated inhibition of HCC cells proliferation, migration and invasion in vitro. Taken together, our data demonstrate that hsa-miR-599 acts as a tumor suppressor and inhibits HCC cells proliferation, migration and invasion by partly targeting oncogenic MYC, which hints that hsa-miR-599 can be a diagnostic and therapeutic biomarker in HCC.
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tian
authors.affiliation: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300193, P. R. China.
authors.forename: Xibao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, NanKai Hospital Tianjin 300100, P. R. China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Tianjin University of Traditional Chinese Medicine Tianjin 300193, P. R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yuan
keywords: Hsa-miR-599; MYC; hepatocellular carcinoma; suppressor