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

J Hematol Oncol. 2019 Jan 9;12(1):3. doi: 10.1186/s13045-018-0690-5.

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.

Keywords: Colorectal cancer; EZH2; SNHG6; ceRNA; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Cytoplasm / metabolism
  • Disease-Free Survival
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism*
  • Sp1 Transcription Factor / metabolism
  • Transcriptome
  • Transfection

Substances

  • Biomarkers, Tumor
  • MIRN214 microRNA, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Sp1 Transcription Factor
  • Sp1 protein, human
  • long non-coding RNA SNHG6, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein