Urology, Jiangxi cancer hospital, Nanchang, 330029, Jiangxi, China.
Cell Death Dis. 2020 May 23;11(5):393. doi: 10.1038/s41419-020-2569-y.
Prostate cancer (PC) is a prevalent male malignancy with high occurrence rate. Recent studies have showed that small nucleolar host genes (SNHGs) and their homolog small nucleolar RNAs (snoRNAs) elicit regulatory functions in carcinogenesis. Present study aimed to investigate the role of SNHG17 and its homolog SNORA71B in PC. Function of SNHG17 and SNORA71B in PC is detected by CCK-8, colony formation, flow cytometry analysis of apoptosis, and transwell migration assay. The mechanism whereby SNHG17 regulated SNORA71B was detected by RIP, pulldown, ChIP, and luciferase reporter assays. Results depicted that transcript 6 of SNHG17 and SNORA71B were upregulated in PC. Knockdown of SNHG17 or SNORA71B weakened proliferation, invasion, migration, and epithelial-to-mesenchymal transition (EMT) and strengthened apoptosis. Mechanistically, SNHG17 and SNORA71B were transcriptionally activated by signal transducer and activator of transcription 5A (STAT5A). SNHG17 positively regulated SNORA71B in PC cell lines and other cell lines. SNHG17 sponged miR-339-5p to upregulate STAT5A and therefore to cause transactivation of SNORA71B. Rescue experiments delineated that SNORA71B was required for the regulation of SNHG17 on PC. Moreover, SNHG17 silence hindered tumorigenesis of PC in vivo. In conclusion, current study first revealed that lncRNA SNHG17 aggravated prostate cancer progression through regulating its homolog SNORA71B via a positive feedback loop, which might do help to the pursuit of better PC treatment.
前列腺癌（PC）是一种常见的男性恶性肿瘤，发病率很高。最近的研究表明，小核仁宿主基因（SNHGs）及其同源小核仁 RNA（snoRNAs）在致癌作用中发挥调节功能。本研究旨在探讨 SNHG17 及其同源物 SNORA71B 在 PC 中的作用。通过 CCK-8、集落形成、细胞凋亡流式细胞术分析和 Transwell 迁移实验检测 SNHG17 和 SNORA71B 在 PC 中的作用。通过 RIP、下拉、ChIP 和荧光素酶报告基因实验检测 SNHG17 调节 SNORA71B 的机制。结果表明，SNHG17 和 SNORA71B 的转录本 6 在 PC 中上调。敲低 SNHG17 或 SNORA71B 减弱了增殖、侵袭、迁移和上皮-间充质转化（EMT），并增强了凋亡。机制上，SNHG17 和 SNORA71B 被信号转导和转录激活因子 5A（STAT5A）转录激活。SNHG17 在 PC 细胞系和其他细胞系中正向调节 SNORA71B。SNHG17 通过海绵 miR-339-5p 上调 STAT5A，从而导致 SNORA71B 的转录激活。挽救实验表明，SNORA71B 是 SNHG17 对 PC 调节所必需的。此外，SNHG17 沉默抑制了 PC 的体内致瘤性。总之，本研究首次揭示，lncRNA SNHG17 通过正反馈环调节其同源物 SNORA71B，从而加剧前列腺癌的进展，这可能有助于寻求更好的前列腺癌治疗方法。
