Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China; Department of Urology, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China; Department of Urology, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
Biochem Biophys Res Commun. 2019 Dec 10;520(3):586-593. doi: 10.1016/j.bbrc.2019.09.108. Epub 2019 Oct 14.
Accepted as crucial participators in human malignancies, long noncoding RNAs (lncRNAs) have been proven to exert significant function on the complicated processes of cancer progression. Although existing investigations have revealed the oncogenic role of lncRNA SOX2 overlapping transcript (SOX2-OT) in different kinds of cancers, such as osteosarcoma and cholangiocarcinoma, the potential role of it in prostate cancer (PC) is poorly understood. This study was the first attempt to decipher the underlying regulatory mechanism of SOX2-OT in PC. According to the data from this study, SOX2-OT expression was conspicuously elevated in PC tissues and cells. Silenced SOX2-OT could repress PC cell proliferation and migration. Besides, mechanism assays manifested that SOX2-OT bound with miR-369-3p and negatively correlated with miR-369-3p in PC. Additionally, miR-369-3p was confirmed to elicit suppressive impact on PC progression. What's more, cofilin 2 (CFL2) was testified to be a downstream target gene of miR-369-3p. Final rescue tests uncovered that CFL2 upregulation or miR-369-3p inhibition could largely restore SOX2-OT knockdown-mediated function on PC progression. To sum up, SOX2-OT accelerates cell proliferation and migration by targeting miR-369-3p/CFL2 axis in PC.
长链非编码 RNA（lncRNA）已被证实作为人类恶性肿瘤的关键参与者，在癌症进展的复杂过程中发挥重要作用。虽然现有研究已经揭示了 lncRNA SOX2 重叠转录物（SOX2-OT）在不同类型的癌症中的致癌作用，如骨肉瘤和胆管癌，但它在前列腺癌（PC）中的潜在作用仍知之甚少。本研究首次尝试解析 SOX2-OT 在 PC 中的潜在调控机制。根据本研究的数据，SOX2-OT 在 PC 组织和细胞中表达明显升高。沉默 SOX2-OT 可以抑制 PC 细胞的增殖和迁移。此外，机制研究表明，SOX2-OT 与 miR-369-3p 结合，并在 PC 中与 miR-369-3p 呈负相关。此外，miR-369-3p 被证实对 PC 进展具有抑制作用。更重要的是，丝切蛋白 2（CFL2）被证明是 miR-369-3p 的下游靶基因。最终的挽救试验表明，CFL2 的上调或 miR-369-3p 的抑制可以在很大程度上恢复 SOX2-OT 敲低对 PC 进展的功能。总之，SOX2-OT 通过靶向 miR-369-3p/CFL2 轴促进 PC 细胞的增殖和迁移。
