Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. P21-activated kinase 4 (PAK4) and miR-9-5p have emerged as attractive therapeutic targets in several tumor types, but in CRC, the regulation of their biological function and their target association remain unclear. The expression of PAK4 in CRC tissues was determined using quantitative real-time PCR and immunohistochemistry analyses. The targeted regulation between miR-9-5p and PAK4 was predicted and confirmed with bioinformatics analysis and the dual-luciferase reporter assay. Functional experiments, including the MTT assay and flow cytometry, were performed to investigate the impact of PAK4 knockdown and miR-9-5p overexpression on cell proliferation and apoptosis in CRC cells. We found that the expression of PAK4 was upregulated in CRC tissues. PAK4 knockdown significantly suppressed cell proliferation and promoted apoptosis in cells of the CRC cell lines HCT116 and SW1116. We also found that miR-9-5p directly targeted the 3′-UTR of PAK4 mRNA and negatively regulated its expression. The degree of downregulation of miR-9-5p inversely correlated with PAK4 expression. Intriguingly, enforced expression of miR-9-5p suppressed cell proliferation and promoted apoptosis. This could be partially reversed by PAK4 overexpression. These results suggest that miR-9-5p targeting of PAK4 could have therapeutic potential for CRC treatment.

中文翻译：

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PAK4 是 miR-9-5p 的靶标，在结直肠癌中促进细胞增殖并抑制细胞凋亡。

结直肠癌 (CRC) 是全球癌症相关死亡的主要原因。P21 激活激酶 4 (PAK4) 和 miR-9-5p 已成为几种肿瘤类型中有吸引力的治疗靶点，但在 CRC 中，其生物学功能的调节及其靶标关联仍不清楚。使用定量实时 PCR 和免疫组织化学分析确定 CRC 组织中 PAK4 的表达。通过生物信息学分析和双荧光素酶报告基因分析预测和证实了 miR-9-5p 和 PAK4 之间的靶向调节。进行了功能实验，包括 MTT 测定和流式细胞术，以研究 PAK4 敲低和 miR-9-5p 过表达对 CRC 细胞增殖和凋亡的影响。我们发现 PAK4 的表达在 CRC 组织中上调。PAK4 敲低显着抑制了 CRC 细胞系 HCT116 和 SW1116 的细胞增殖并促进了细胞凋亡。我们还发现 miR-9-5p 直接靶向 PAK4 mRNA 的 3'-UTR 并负调控其表达。miR-9-5p的下调程度与PAK4的表达呈负相关。有趣的是，miR-9-5p 的强制表达抑制了细胞增殖并促进了细胞凋亡。这可以通过 PAK4 过表达部分逆转。这些结果表明，靶向 PAK4 的 miR-9-5p 可能具有治疗 CRC 的潜力。miR-9-5p的下调程度与PAK4的表达呈负相关。有趣的是，miR-9-5p 的强制表达抑制了细胞增殖并促进了细胞凋亡。这可以通过 PAK4 过表达部分逆转。这些结果表明，靶向 PAK4 的 miR-9-5p 可能具有治疗 CRC 的潜力。miR-9-5p的下调程度与PAK4的表达呈负相关。有趣的是，miR-9-5p 的强制表达抑制了细胞增殖并促进了细胞凋亡。这可以通过 PAK4 过表达部分逆转。这些结果表明，靶向 PAK4 的 miR-9-5p 可能具有治疗 CRC 的潜力。