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

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 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.

Integrated grade-wise profiling analysis reveals potential plasma miR-373-3p as prognostic indicator in Prostate Cancer & its target KPNA2

“…Moreover, miR-373-3p regulates proliferation through the amyloid precursor protein (APP) in lung adenocarcinoma patients [ 33 ]. Another finding suggested that SNHG16 stimulated cell proliferation and migration by activating the miR-373-3p/TGF R2/SMAD axis in PCa patients [ 34 ]. Qiu et al revealed that the inhibition of miR-373-3p by TR4 may serve as a suppressor function, causing changes in TGFR2/p-Smad3 expression and thereby promoting PCa metastasis [ 35 ].…”

Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer

“…An exactly similar scenario has been described for the small nucleolar RNA host gene 3 ( SNHG3 ), which enhanced TGFBR1 mRNA expression by sponging away the negative regulation exerted by miR-214-3p ( 89 ). An equivalent ceRNA-mediated mechanism seems to involve regulation of TGFBR2 and involves the small nucleolar RNA host gene 16 ( SNHG16 ) lncRNA, which is highly expressed in prostate carcinoma tissue and cells ( 90 ). High SNHG16 expression seems to sponge and inactivate miR-373-3p , which can downregulate the TGFBR2 mRNA.…”

“…High SNHG16 expression seems to sponge and inactivate miR-373-3p , which can downregulate the TGFBR2 mRNA. Thus, in prostate cancer cells with high SNHG16 expression, TGFβRII protein levels increased, causing enhanced TGF-β signaling that facilitated cancer invasiveness ( 90 ). Keeping in the same mode of action, DANCR expression correlated with Gleason score and prostate-specific antigen levels in the serum of prostate cancer patients ( 91 ).…”

Roles of TGF‑β signalling pathway‑related lncRNAs in cancer (Review)

“…In prostate cancer, SNHG16 promotes proliferation and migration of prostate cancer cells by targeting the TGF-βRII/SMAD axis ( 113 ).…”