Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR-137.

Yang Fu,Xiefu Zhang,Yanru Qin,Yiyu Qin,Yuhan Yin,Changqing Guo,Yang Yu,Ge Yang,Wen Xu,Sanfei Peng

doi:10.1002/mc.23101

Abstract

Small nucleolar RNA host gene 1 (SNHG1) is critical in the progression of cancers. However, the mechanism by which SNHG1 regulates the progression of colorectal cancer (CRC) remains unclear. Expressions of SNHG1 and miR‐137 in CRC tissues and cell lines were evaluated by quantitative real‐time polymerase chain reaction. A luciferase reporter gene assay was conducted to investigate miR‐137 target. Additionally, RNA pull‐down assay was performed to explore the physical association between miR‐137, SNHG1, and RNA induced silencing complex (RISC). Cell cycling and invasion were examined by flow cytometry (FCM) and transwell assays. The in vivo carcinogenic activity of SNHG1 was examined using murine xenograft models. Expression of RICTOR, serine/threonine kinase 1 (AKT), serum and glucocorticoid‐inducible kinase 1 (SGK1), p70S6K1, and LC3II/LC3I ratio was examined by Western blot analysis. SNHG1 upregulation was observed in CRC tissues and cell lines, which was associated with the lymph node metastasis, advanced TNM stage and poorer prognosis. SNHG1 increased RICTOR level in CRC via sponging miR‐137. In addition, SNHG1 silencing inhibited CRC cell proliferation and migration in vitro and in vivo. SNHG1 regulated RICTOR expression by sponging miR‐137 and promoted tumorgenesis in CRC.

Highlights

Colorectal cancer (CRC) is the third most common malignant tumor in humans, and is the most common malignant gastrointestinal tumor.[1]
The competing endogenous RNA (CeRNA) hypothesis was proposed. This suggests that a large number of noncoding RNAs (ncRNAs) types may interact with and sequester miRNAs, thereby derepressing the function of alternate and unsequestered transcripts of these miRNAs, providing a novel mechanism contributing to posttranscriptional regulation of target genes.[5,6]
It is known that long noncoding RNAs (lncRNAs) play functional roles in a series of steps during tumor development, and they may interact with DNA, RNA, protein and/or various combinations to act as important regulators of chromatin organization and transcriptional as well as posttranscriptional regulation.[21]

Summary

| INTRODUCTION

Colorectal cancer (CRC) is the third most common malignant tumor in humans, and is the most common malignant gastrointestinal tumor.[1]. The competing endogenous RNA (CeRNA) hypothesis was proposed This suggests that a large number of ncRNA types may interact with and sequester miRNAs, thereby derepressing the function of alternate and unsequestered transcripts of these miRNAs, providing a novel mechanism contributing to posttranscriptional regulation of target genes.[5,6]. LncRNA‐HULC overexpression may suppress miR‐186 expression, resulting in increased expression of its target protein, HMGA2, which serves as an oncogene in hepatocellular carcinoma.[9]. Such mRNA/miR‐lncRNA coregulatory pairs (eg, TCF7L2/miR‐217‐CRNDE and TUSC7/miR‐211‐CDK6) have been demonstrated in CRC.[10,11]. Based on the above results, SNHG1 possesses the characteristics of an oncogene in many tumor types; the role of SNHG1 in CRC remains unclear It has been documented that SNHG1 promoted the growth of primary esophageal cancer, hepatocellular carcinoma, and non‐small–cell lung cancer via sponging several tumor‐suppressive miRNAs including miR‐338, miR‐195, and miR‐101‐3p.12,16,17 Based on the above results, SNHG1 possesses the characteristics of an oncogene in many tumor types; the role of SNHG1 in CRC remains unclear

| MATERIALS AND METHODS

I‐II III‐IV

Findings

| DISCUSSION

| CONCLUSION