Inhibition of microRNA-500 has anti-cancer effect through its conditional downstream target of TFPI in human prostate cancer.
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.
['Cai|Bing|B|', 'Chen|Wei|W|', 'Pan|Yue|Y|', 'Chen|Hongde|H|', 'Zhang|Yirong|Y|', 'Weng|Zhiliang|Z|', 'Li|Yeping|Y|http://orcid.org/0000-0003-0297-5365']
D000368:Aged D017209:Apoptosis D063646:Carcinogenesis D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D015536:Down-Regulation D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008074:Lipoproteins D008297:Male D035683:MicroRNAs D008875:Middle Aged D011379:Prognosis D011467:Prostate D011471:Prostatic Neoplasms
TFPI prostate miR-500 cancer proliferation biomarker cancer migration