Long non-coding RNA SNHG6 increases JAK2 expression by targeting the miR-181 family to promote colorectal cancer cell proliferation

J Gene Med. 2020 Dec;22(12):e3262. doi: 10.1002/jgm.3262. Epub 2020 Sep 21.

Abstract

Background: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) exerts a regulatory role in cancer biology, although its detailed functions and mechanisms in colorectal cancer (CRC) still remain unclear.

Methods: A quantitative reverse transcriptase-polymerase chain reaction was implemented to investigate the expression of SNHG6, miR-181 family and Janus kinase 2 (JAK2) in CRC tissues and cell lines. The proliferation of CRC cells was detected by a cell counting kit-8 assay, and the apoptosis of CRC cells was determined by flow cytometry analysis. The interaction of the miR-181 family with SNHG6 or with the 3'-untranslated region of JAK2 was validated by the luciferase reporter gene method. The effects of SNHG6 and the miR-181 family on JAK2 expression were analyzed by western blotting.

Results: SNHG6 was significantly up-regulated in CRC samples. The knockdown of SNHG6 reduced the proliferation of CRC cells and promoted the apoptosis, whereas the over-expression of SNHG6 had the opposite effect. SNHG6 could bind with all the four members of the miR-181 family, and expression in miR-181 family members was significantly down-regulated in CRC samples. SNHG6 expression was negatively correlated with the miR-181 family member expression in CRC samples. Moreover, over-expressed SNHG6 significantly counteracted the inhibitory effect of miR-181 mimics on CRC cell proliferation, as well as the promoting effect on apoptosis. Furthermore, SNHG6 over-expression and knockdown can promote and inhibit JAK2 expression, respectively, and miR-181 family member function is opposite to that of SNHG6 by repressing JAK2.

Conclusions: SNHG6 can exert a cancer-promoting effect in CRC by targeting miR-181 family members and up-regulating JAK2.

Keywords: JAK2; SNHG6; colorectal cancer; miR-181 family; proliferation.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIrn181 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA SNHG6, human
  • JAK2 protein, human
  • Janus Kinase 2