Cai Bing, Chen Wei, Pan Yue, Chen Hongde, Zhang Yirong, Weng Zhiliang, Li Yeping
Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Prostate. 2017 Jul;77(10):1057-1065. doi: 10.1002/pros.23361. Epub 2017 Jun 20.
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.
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.
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.
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.
我们研究了微小RNA-500（miR-500）以及组织因子途径抑制剂（TFPI）人类基因在前列腺癌中的预后潜力和调控机制。
通过qRT-PCR评估前列腺癌细胞系和原发性肿瘤中miR-500的表达。根据内源性miR-500水平分析癌症患者的临床病理因素和总生存期。在DU145和VCaP细胞中下调miR-500。探讨其对前列腺癌增殖、体外侵袭及体内致瘤性的影响。通过荧光素酶测定和qRT-PCR评估前列腺癌细胞中miR-500可能的下游靶点TFPI。在miR-500下调的DU145和VCaP细胞中沉默TFPI，以观察其是否直接参与前列腺癌中miR-500的调控。在DU145和VCaP细胞中单独上调或下调TFPI。进一步评估它们对前列腺癌发展的影响。
miR-500在前列腺癌细胞和原发性肿瘤中均上调。在前列腺癌患者中，高miR-500表达与不良预后和总生存期相关。在DU145和VCaP细胞中，miR-500下调抑制了癌症增殖、体外侵袭及体内外植体生长。在前列腺癌中，TFPI被证实与miR-500相关。TFPI下调逆转了miR-500下调对前列腺癌细胞的抗癌作用。然而，单独上调或下调TFPI对前列腺癌发展均无功能影响。
miR-500可能是前列腺癌的潜在生物标志物和分子靶点。在miR-500下调的前列腺癌细胞中，TFPI可能对前列腺癌具有条件性调控作用。
