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

• DOI: 10.1186/s13045-018-0690-5
• Publication Date: 2019-01-09T12:42:38Z
• Authors: Mu Xu; Xiaoxiang Chen; Kang Lin; Kaixuan Zeng; Xiangxiang Liu; Xueni Xu; Bei Pan; Tao Xu; Li Sun; Bangshun He; Yuqin Pan; Huiling Sun; Shukui Wang
• Keywords: Male; 0301 basic medicine; Cytoplasm; Mice, Nude; Disease-Free Survival; Mice; 03 medical and health sciences; Cell Movement; SNHG6; Biomarkers, Tumor; Animals; Humans; Diseases of the blood and blood-forming organs; Enhancer of Zeste Homolog 2 Protein; EZH2; RC254-282; Cell Proliferation; Mice, Inbred BALB C; microRNA; Base Sequence; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; ceRNA; Middle Aged; HCT116 Cells; Colorectal cancer; 3. Good health; MicroRNAs; Heterografts; Female; RC633-647.5; Colorectal Neoplasms; HT29 Cells

Abstract Background 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.

Methods We 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.

Results We 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.

Conclusions Our study elucidated that SNHG6 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.