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MicroRNA-335 在前列腺癌中作为候选肿瘤抑制因子发挥作用。

MicroRNA-335 acts as a candidate tumor suppressor in prostate cancer.

机构信息

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.

出版信息

Pathol Oncol Res. 2013 Jul;19(3):529-37. doi: 10.1007/s12253-013-9613-5. Epub 2013 Mar 3.

Abstract

MicroRNA-335 (miR-335) acts as a tumor suppressor or a tumor promoter in different human malignancies. However, the involvement of miR-335 in prostate cancer (PCa) is still unclear. The purpose of this study was to investigate the functional and clinical significance of miR-335 in PCa. miR-335 expression in 3 PCa cell lines (LNCaP/DU145/PC3) and in 20 clinical PCa tissues were detected by real-time quantitative reverse transcriptase-PCR compared with corresponding controls. The function of miR-335 was investigated for cell proliferation, invasion and migration in PCa cells transfected with agents containing EGFP-miR-335 expression vector. Additionally, miR-335 expression in 104 clinical PCa tissues was detected by in situ hybridization. Its assocaitions with clinicopathological features and prognosis in patients with PCa were also determined. miR-335 was significantly down-regulated in PCa cell lines than in the normal prostate cell line (P < 0.01). With the similar results in vitro, the reduced expression of miR-335 was also found in human PCa tissues comparing with paired adjacent benign prostate tissues (P < 0.05). Moreover, the increased expression of miR-335 suppressed cell proliferation, invasion and migration of PCa cell lines in vitro. Turning to its clinical significance, the low expression of miR-335 was significantly associated with high Gleason Score (P = 0.04), advanced clinical stage (P = 0.04), and positive metastasis (P = 0.02), but not with prognosis in PCa patients. Our data demonstrated for the first time the inhibitory effect of miR-335 on cell proliferation and invasion for PCa cells. The loss of this microRNA might be associated with clinical progression of PCa patients.

摘要

微小 RNA-335(miR-335)在不同的人类恶性肿瘤中作为肿瘤抑制因子或肿瘤促进因子发挥作用。然而,miR-335 在前列腺癌(PCa)中的作用仍不清楚。本研究旨在探讨 miR-335 在 PCa 中的功能和临床意义。通过实时定量逆转录 PCR 检测 3 种 PCa 细胞系(LNCaP/DU145/PC3)和 20 例临床 PCa 组织中的 miR-335 表达,与相应对照进行比较。通过转染含有 EGFP-miR-335 表达载体的试剂,研究 miR-335 在 PCa 细胞中的增殖、侵袭和迁移功能。此外,通过原位杂交检测 104 例临床 PCa 组织中的 miR-335 表达。还确定了 miR-335 在 PCa 患者的临床病理特征和预后中的相关性。miR-335 在 PCa 细胞系中的表达明显低于正常前列腺细胞系(P < 0.01)。在体外具有相似的结果,与配对的相邻良性前列腺组织相比,人 PCa 组织中 miR-335 的表达也降低(P < 0.05)。此外,miR-335 的表达增加抑制了 PCa 细胞系在体外的增殖、侵袭和迁移。就其临床意义而言,miR-335 的低表达与高 Gleason 评分(P = 0.04)、晚期临床分期(P = 0.04)和阳性转移(P = 0.02)显著相关,但与 PCa 患者的预后无关。我们的数据首次证明了 miR-335 对 PCa 细胞增殖和侵袭的抑制作用。这种微小 RNA 的丢失可能与 PCa 患者的临床进展有关。

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