Long non­‑coding RNA SNHG16 functions as a tumor activator by sponging miR‑373‑3p to regulate the TGF‑β‑R2/SMAD pathway in prostate cancer

Weng,Wubin; Liu,Changming; Li,Guomin; Ruan,Qiongfang; Li,Huizhang; Lin,Ningfeng; Chen,Guangbing

doi:10.3892/mmr.2021.12483

Long non‑coding RNA SNHG16 functions as a tumor activator by sponging miR‑373‑3p to regulate the TGF‑β‑R2/SMAD pathway in prostate cancer

Authors:
- Wubin Weng
- Changming Liu
- Guomin Li
- Qiongfang Ruan
- Huizhang Li
- Ningfeng Lin
- Guangbing Chen
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Affiliations: 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
Published online on: October 11, 2021 https://doi.org/10.3892/mmr.2021.12483
Article Number: 843

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Abstract

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 mechanisms 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.

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