Title |
Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma
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Published in |
Journal of Experimental & Clinical Cancer Research, November 2017
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DOI | 10.1186/s13046-017-0622-1 |
Pubmed ID | |
Authors |
Yanping Gao, Jun Yi, Kai Zhang, Fan Bai, Bing Feng, Rui Wang, Xiaoyuan Chu, Longbang Chen, Haizhu Song |
Abstract |
Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC. Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels. We investigated the role of miR-31 in the regulation of LATS2 expression in ESCC cell lines via functional assays both in vivo and in vitro. The luciferase reporter assays was conducted to confirm LATS2 is a potential target of miR-31. Immunohistochemistry was used to measure LATS2 and TAZ expression in normal and ESCC tissue. LATS2 is a component of the Hippo tumor-suppressive signaling pathway. Frequent loss of heterozygosity of LATS2 has been reported in esophageal cancer. We analyzed the reciprocal expression regulation of miR-31 and LATS2 and demonstrated that LATS2 expression was elevated by down-regulation of miR-31 at the post-transcriptional level in ESCC. Moreover, miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR, a key molecule in the Hippo pathway. Then, LATS2 consequently promoted the translocation of TAZ, which was examined using immunohistochemistry. Silencing of miR-31 significantly inhibited the cell proliferation, induced apoptosis and decreased the ability of migration/invasion in vitro. LATS2 impedes ESCC cell proliferation and invasion by suppressing miR-31, as well as mice xenograft model in vivo. Meanwhile, the nuclear localization of LATS2 constrained the phosphorylation of TAZ. Then, the expression level of TAZ was notably heightened with a high risk of recurrence compared to that observed in the low-risk patients, as well as, the higher expression associated with a poor survival. Our study demonstrated that overexpression of miR-31 undertook an oncogenic role in ESCC by repressing expression of LATS2 via the Hippo Pathway and activating epithelial-mesenchymal transition. LATS2 and TAZ could be potential novel molecular markers for predicting the risk of recurrence and prognosis of ESCC. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 3 | 18% |
Student > Doctoral Student | 2 | 12% |
Student > Bachelor | 2 | 12% |
Librarian | 1 | 6% |
Other | 1 | 6% |
Other | 3 | 18% |
Unknown | 5 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 4 | 24% |
Biochemistry, Genetics and Molecular Biology | 3 | 18% |
Social Sciences | 2 | 12% |
Unspecified | 1 | 6% |
Engineering | 1 | 6% |
Other | 0 | 0% |
Unknown | 6 | 35% |