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Inhibition of microRNA‐500 has anti‐cancer effect through its conditional downstream target of TFPI in human prostate cancer
Author(s) -
Cai Bing,
Chen Wei,
Pan Yue,
Chen Hongde,
Zhang Yirong,
Weng Zhiliang,
Li Yeping
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23361
Subject(s) - du145 , prostate cancer , downregulation and upregulation , cancer , cancer research , cancer cell , prostate , medicine , microrna , oncology , biology , lncap , biochemistry , gene
Purpose We investigated the prognostic potential and regulatory mechanism of microRNA‐500 (miR‐500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. Methods MiR‐500 expression was assessed by qRT‐PCR in prostate cancer cell lines and primary tumors. Cancer patients’ clinicopathological factors and overall survival were analyzed according to endogenous miR‐500 level. MiR‐500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed. Possible downstream target of miR‐500, TFPI was assessed by luciferase assay and qRT‐PCR in prostate cancer cells. In miR‐500‐downregulated DU145 and VCaP cells, TFPI was silenced to see whether it was directly involved in the regulation of miR‐500 in prostate cancer. TFPI alone was either upregulated or downregulated in DU145 and VCaP cells. Their effect on prostate cancer development was further evaluated. Results MiR‐500 is upregulated in both prostate cancer cells and primary tumors. In prostate cancer patients, high miR‐500 expression is associated with poor prognosis and overall survival. In DU145 and VCaP cells, miR‐500 downregulation inhibited cancer proliferation, invasion in vitro, and explant growth in vivo. TFPI was verified to be associated with miR‐500 in prostate cancer. Downregulation of TFPI reversed anti‐cancer effects of miR‐500 downregulation in prostate cancer cells. However, neither TFPI upregulation nor downregulation alone had any functional impact on prostate cancer development. Conclusion MiR‐500 may be a potential biomarker and molecular target in prostate cancer. TFPI may conditionally regulate prostate cancer in miR‐500‐downregualted prostate cancer cells.