LncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer

Mu Xu,Kang Lin,Xiangxiang Liu,Bangshun He,Yuqin Pan,Bei Pan,Xiaoxiang Chen,Kaixuan Zeng,Huiling Sun,Xueni Xu,Li Sun,Shukui Wang,Tao Xu

doi:10.1186/s13045-018-0690-5

Abstract

BackgroundAbnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets.MethodsWe analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer (CRC). The functions of small nucleolar RNA host gene 6 (SNHG6) were investigated through in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, wound healing assay, transwell assay, and xenograft model). The mechanism of action of SNHG6 was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay, and RNA immunoprecipitation assay.ResultsWe identified aberrantly expressed lncRNAs in CRC. We found that elevated SNHG6 expression was associated with poor prognosis and CRC progression. We also demonstrated that the high SNHG6 expression was partly due to DNA copy number gains and SP1 induction. Functional studies showed that SNHG6 promoted CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, we found that SNHG6 expressed predominantly in the cytoplasm. SNHG6 could interact with miR-26a, miR-26b, and miR-214 and regulate their common target EZH2.ConclusionsOur study elucidated that SNHG6 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.

Highlights

Abnormal expression of long non-coding RNAs has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets
We detected small nucleolar RNA host gene 6 (SNHG6) expression in 80 paired colorectal cancer tissue and adjacent normal tissue samples by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and SNHG6 expression was significantly upregulated in 88.8%
To explore the clinical relevance of SNHG6 in colorectal cancer (CRC), we divided the enrolled patients into two groups according to SNHG6 expression

Summary

Introduction

Abnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets. There is a high frequency of recurrence and metastasis in CRC patients, even among those who undergo surgical resection. These factors contribute to the poor prognosis of CRC [3]. Long noncoding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with limited or no protein-coding potential. They have attracted increasing attention, because a growing number of studies have suggested that they were involved in many physiological and pathological processes, such as cell

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