LncRNA SNHG17 promotes tumor progression and predicts poor survival in human renal cell carcinoma via sponging miR-328-3p.

Jie Wu,Shaojin Zhang,Gang Dong,Lulu Sun,Tingting Liu,Weijie Liang

doi:10.18632/aging.203440

Abstract

Accumulating data shows that dysregulation of long non-coding RNAs (lncRNAs) are involved in human tumors' occurrence and progression. Small nucleolar RNA host genes (SNHGs) are recently revealed to play a carcinogenic role in various human neoplasms. However, the functions and underlying mechanisms of lncRNA SNHG17 in renal cell carcinoma (RCC) are still elusive. We analyzed the relationship between SNHG17 expression levels and clinicopathologic characteristics and prognosis in patients with RCC according to TCGA RNA-sequencing data and our cohort data. Loss-of-function and gain-of-function experiments were conducted to examine the biological behaviors of SNHG17 on RCC cell proliferation, migration, invasion, apoptosis, and tumor growth in vivo. The interaction between SNHG17, miR-328-3p, and Histone’sH2Avariant (H2AX) was verified by bioinformatics, dual-luciferase reporter gene, and RNA immunoprecipitation (RIP). Highly expressed SNHG17 was evident in RCC tissue samples and cell lines, and SNHG17 overexpression was related to advanced TNM stage and reduced relapse-free and overall survival of patients with RCC. Knockdown of SNHG17 prohibited malignant phenotypes, whereas ectopic SNHG17 expression showed the opposite effects. More importantly, SNHG17 could upregulate the expression of H2AX by acting as a miR-328-3p sponge. In vivo experiments confirmed that SNHG17 promoted the growth of RCC tumors. SNHG17/miR-328-3p/H2AXaxis might be involved in RCC progression, which provided a potential therapeutic target for RCC.

Highlights

Clear cell renal cell carcinoma represents the most common histological subtype of RCC, accounting for approximately 3% of all adult cancers. [1] RCC is characterized by a high rate of relapse and metastasis, which exerts a socio-economic burden on society and patients' families
Highly expressed small nuclear RNA host gene 17 (SNHG17) was evident in RCC tissue samples and cell lines, and SNHG17 overexpression was related to advanced TNM stage and reduced relapse-free and overall survival of patients with RCC
SNHG17/miR-328-3p/H2AX axis might be involved in RCC progression, which provided a potential therapeutic target for RCC

Summary

Introduction

Clear cell renal cell carcinoma (ccRCC) represents the most common histological subtype of RCC, accounting for approximately 3% of all adult cancers. [1] RCC is characterized by a high rate of relapse and metastasis, which exerts a socio-economic burden on society and patients' families. More than 90% of the human genome is transcribed to non-coding RNA (ncRNA) Among these ncRNAs, long ncRNAs (lncRNAs) of > 200 nt in length have been well studied in the development and invasion of human malignancies. [6, 7] LncRNAs exert oncogenic or suppressive functions in various human cancers, including RCC.[8,9,10] LncRNA small nuclear RNA host gene 17 (SNHG17) is located on 20q11.23, with a 1,186 nt in length. Aberrant expression of SNHG17 has been suggested to play vital roles in the development and progression of human carcinomas, such as gastric cancer, prostate cancer, non-small cell lung cancer (NSCLC), and breast cancer, etc.[11,12,13,14] to the best of our knowledge, the biological roles and underlying molecular mechanisms of SNHG17 in RCC remain unclarified. The functions and underlying mechanisms of lncRNA SNHG17 in renal cell carcinoma (RCC) are still elusive

Methods

Results

Conclusion