Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2019 May;19(5):4407-4418. doi: 10.3892/mmr.2019.10065. Epub 2019 Mar 21.
MicroRNAs (miRs) are small non‑coding RNA molecules that regulate gene expression at the post‑transcriptional level. Aberrant expression of miR‑9 has been reported to be involved in the tumorigenesis and progression of various malignancies. However, its role in prostate cancer (PC) has not been completely clarified. In the present study, miR‑9 expression was examined in different PC cell lines, patient tissues and a mouse model. Cell Counting Kit‑8 and BrdU immunofluorescence assays were performed to assess the effect of miR‑9 on the viability of PC cells, while Transwell and wound‑healing assays were utilized to evaluate the migration and invasion of PC cells expressing miR‑9. Furthermore, a dual‑luciferase reporter assay was performed to verify whether mitogen‑activated protein kinase kinase kinase 3 (MEKK3) was a direct target of miR‑9. The results demonstrated significant downregulation of miR‑9 expression in different PC cell lines and 31 human PC tissues, as compared with that in a normal prostate cell line and adjacent normal tissues, respectively. By contrast, upregulation of MEKK3 was confirmed in human PC tissue samples, with its level inversely associated with miR‑9 expression. Overexpression of miR‑9 in six different PC cell lines (DU145, LNCaP, 22Rv1, PC‑3, C4‑2B and VCaP) reduced the cell viability and migration. Furthermore, it was demonstrated that the 3'‑untranslated region of MEKK3 was a target of miR‑9, and that MEKK3 overexpression prevented the inhibitory effects of miR‑9 on the viability, migration and invasion of PC cells. miR‑9 overexpressing tumor cells also exhibited growth delay in comparison with control tumor cells in vivo. Taken together, the current study findings provided novel insights into the underlying molecular mechanisms of PC oncogenesis, which may support the development of new therapeutic approaches for the treatment of PC.
微小 RNA（miRs）是一种小的非编码 RNA 分子，可在转录后水平调节基因表达。据报道，miR-9 的异常表达与多种恶性肿瘤的发生和发展有关。然而，其在前列腺癌（PC）中的作用尚未完全阐明。在本研究中，检测了不同 PC 细胞系、患者组织和小鼠模型中的 miR-9 表达。通过细胞计数试剂盒-8 和 BrdU 免疫荧光测定评估 miR-9 对 PC 细胞活力的影响，而 Transwell 和划痕愈合测定用于评估表达 miR-9 的 PC 细胞的迁移和侵袭。此外，还进行了双荧光素酶报告基因测定以验证丝裂原活化蛋白激酶激酶激酶 3（MEKK3）是否是 miR-9 的直接靶标。结果表明，与正常前列腺细胞系和相邻正常组织相比，不同的 PC 细胞系和 31 个人类 PC 组织中 miR-9 的表达明显下调。相比之下，在人类 PC 组织样本中证实了 MEKK3 的上调，其水平与 miR-9 的表达呈负相关。在六种不同的 PC 细胞系（DU145、LNCaP、22Rv1、PC-3、C4-2B 和 VCaP）中转染 miR-9 可降低细胞活力和迁移。此外，证明 MEKK3 的 3'非翻译区是 miR-9 的靶标，并且 MEKK3 的过表达可阻止 miR-9 对 PC 细胞活力、迁移和侵袭的抑制作用。与对照肿瘤细胞相比，过表达 miR-9 的肿瘤细胞在体内也表现出生长延迟。总之，本研究结果为 PC 癌发生的潜在分子机制提供了新的见解，可能为 PC 的治疗提供新的治疗方法。
