LINC01088/miR-22/CDC6 轴通过激活 PI3K/AKT 通路调节前列腺癌的进展。
LINC01088/miR-22/CDC6 Axis Regulates Prostate Cancer Progression by Activating the PI3K/AKT Pathway.
机构信息
Department of Urology, Longgang District People's Hospital of Shenzhen, Guangdong 518000, China.
Department of Thyroid and Breast Surgery, Longgang Central Hospital, Shenzhen, Guangdong 518000, China.
出版信息
Mediators Inflamm. 2023 Jul 19;2023:9207148. doi: 10.1155/2023/9207148. eCollection 2023.
BACKGROUND
Prostate cancer (PCa) harms the male reproductive system, and lncRNA may play an important role in it. Here, we report that the LINC01088/microRNA- (miRNA/miR-) 22/cell division cycle 6 (CDC6) axis regulated through the phosphatidylinositide 3-kinases- (PI3K-) protein kinase B (AKT) signaling pathway controls the development of PCa.
METHODS
lncRNA/miRNA/mRNA associated with PCa was downloaded and analyzed by Gene Expression Omnibus. The expression and correlation of LINC01088/miR-22/CDC6 in PCa were analyzed and verified by RT-qPCR. Dual-luciferase was used to analyze the binding between miR-22 and LINC01088 or CDC6. Cell Counting Kit-8 and Transwell were used to analyze the effects of LINC01088/miR-22/CDC6 interactions on PCa cell viability or migration/invasion ability. Localization of LINC01088 in cells was analyzed by nuclear cytoplasmic separation. The effect of LINC01088/miR-22/CDC6 interaction on downstream PI3K/AKT signaling was analyzed by Western blot.
RESULTS
LINC01088 or CDC6 was upregulated in prostate tumor tissues or cells, whereas miR-22 was downregulated, miR-22 directly targets both LINC01088 and CDC6. si-LINC01088 inhibits the PCa process by suppressing the PI3K/AKT pathway. CDC6 reverses si-linc01088-mediated cell growth inhibition and reduction of PI3K and AKT protein levels.
CONCLUSION
Our results demonstrate that the LINC01088/miR-22/CDC6 axis functions in PCa progression and provide a promising diagnostic and therapeutic target.
背景
前列腺癌（PCa）危害男性生殖系统，长链非编码 RNA（lncRNA）可能在其中发挥重要作用。在这里，我们报告 LINC01088/微小 RNA-（miRNA/miR-）22/细胞分裂周期 6（CDC6）轴通过磷脂酰肌醇 3-激酶-（PI3K-）蛋白激酶 B（AKT）信号通路调控，控制 PCa 的发展。
方法
通过基因表达综合数据库下载并分析与 PCa 相关的 lncRNA/miRNA/mRNA。通过 RT-qPCR 分析和验证 PCa 中 LINC01088/miR-22/CDC6 的表达和相关性。双荧光素酶报告基因检测分析 miR-22 与 LINC01088 或 CDC6 的结合。细胞计数试剂盒-8 和 Transwell 用于分析 LINC01088/miR-22/CDC6 相互作用对 PCa 细胞活力或迁移/侵袭能力的影响。通过核质分离分析 LINC01088 在细胞中的定位。通过 Western blot 分析 LINC01088/miR-22/CDC6 相互作用对下游 PI3K/AKT 信号的影响。
结果
LINC01088 或 CDC6 在前列腺肿瘤组织或细胞中上调，而 miR-22 下调，miR-22 直接靶向 LINC01088 和 CDC6。si-LINC01088 通过抑制 PI3K/AKT 通路抑制 PCa 进程。CDC6 逆转了 si-LINC01088 介导的细胞生长抑制和 PI3K 和 AKT 蛋白水平的降低。
结论
我们的结果表明，LINC01088/miR-22/CDC6 轴在 PCa 进展中发挥作用，并为诊断和治疗提供了有前途的靶点。
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