Weng Wubin, Liu Changming, Li Guomin, Ruan Qiongfang, Li Huizhang, Lin Ningfeng, Chen Guangbing
Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, P.R. China.
Department of Respiratory Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, P.R. China.
Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12483. Epub 2021 Oct 13.
Long non‑coding RNAs (lncRNAs) are involved in the pathogenesis of prostate cancer (PCa) as competitive endogenous RNA. The present study aimed to investigate the molecular mech--anisms of lncRNA small nucleolar RNA host gene 16 (SNHG16) in the proliferation and metastasis of PCa cells. Cancer tissues and adjacent normal tissues were collected from 80 patients with PCa who did not receive any treatment. Reverse transcription‑quantitative PCR analysis was performed to detect the expression levels of SNHG16, hsa‑microRNA (miRNA/miR)‑373‑3p and transforming growth factor‑β receptor type 2 (TGF‑β‑R2), and Spearman's correlation coefficient analysis was performed to assess the correlations between these molecules. Furthermore, the effects of SNHG16 knockdown and overexpression on the biological functions of DU‑145 PCa cells and TGF‑β‑R2/SMAD signaling were analyzed. The dual‑luciferase reporter assay was performed to assess the associations between SNHG16 and miR‑373‑3p, and TGF‑β‑R2 and miR‑373‑3p, the effects of which were verified via rescue experiments. The results demonstrated that the expression levels of SNHG16 and TGF‑β‑R2 were significantly upregulated in PCa tissues, whereas miR‑373‑3p expression was significantly downregulated (P<0.001). In addition, negative correlations were observed between SNHG16 and miR‑373‑3p (rho, ‑0.631) and miR‑373‑3p and TGF‑β‑R2 (rho, ‑0.516). Overexpression of SNHG16 significantly promoted the proliferation, migration and invasion of PCa cells (P<0.05), and significantly increased the protein expression levels of TGF‑β‑R2, phosphorylated (p)‑SMAD2, p‑SMAD3, c‑Myc and E2F4 (P<0.001). Notably, the results revealed that miR‑373‑3p is a target of SNHG16, and miR‑373‑3p knockdown rescued short hairpin (sh)‑SNHG16‑suppressed cellular functions by promoting TGF‑β‑R2/SMAD signaling. The results also revealed that miR‑373‑3p targets TGF‑β‑R2. Notably, transfection with miR‑373‑3p inhibitor rescued sh‑TGF‑β‑R2‑suppressed cell proliferation and migration. Taken together, the results of the present study suggest that SNHG16 promotes the proliferation and migration of PCa cells by targeting the miR‑373‑3p/TGF‑β‑R2/SMAD axis.
长链非编码RNA（lncRNAs）作为竞争性内源性RNA参与前列腺癌（PCa）的发病机制。本研究旨在探讨lncRNA小核仁RNA宿主基因16（SNHG16）在PCa细胞增殖和转移中的分子机制。收集80例未接受任何治疗的PCa患者的癌组织及相邻正常组织。采用逆转录-定量PCR分析检测SNHG16、人微小RNA（miRNA/miR）-373-3p和转化生长因子-β受体2型（TGF-β-R2）的表达水平，并进行Spearman相关系数分析以评估这些分子之间的相关性。此外，分析了SNHG16敲低和过表达对DU-145 PCa细胞生物学功能及TGF-β-R2/SMAD信号通路的影响。进行双荧光素酶报告基因分析以评估SNHG16与miR-373-3p、TGF-β-R2与miR-373-3p之间的关联，其作用通过挽救实验得到验证。结果表明，SNHG16和TGF-β-R2在PCa组织中的表达水平显著上调，而miR-373-3p表达显著下调（P<0.001）。此外，SNHG16与miR-373-3p（rho，-0.631）以及miR-373-3p与TGF-β-R2（rho，-0.516）之间存在负相关。SNHG16过表达显著促进PCa细胞的增殖、迁移和侵袭（P<0.05），并显著增加TGF-β-R2、磷酸化（p）-SMAD2、p-SMAD3、c-Myc和E2F4的蛋白表达水平（P<0.001）。值得注意的是，结果显示miR-373-3p是SNHG16的靶标，敲低miR-373-3p通过促进TGF-β-R2/SMAD信号通路挽救了短发夹（sh）-SNHG16抑制的细胞功能。结果还显示miR-373-3p靶向TGF-β-R2。值得注意的是，用miR-373-3p抑制剂转染挽救了sh-TGF-β-R2抑制的细胞增殖和迁移。综上所述，本研究结果表明SNHG16通过靶向miR-373-3p/TGF-β-R2/SMAD轴促进PCa细胞的增殖和迁移。
