lncRNA Gm15290 promotes cell proliferation and invasion in lung cancer through directly interacting with and suppressing the tumor suppressor miR-615-5p

Biosci Rep. 2018 Oct 31;38(5):BSR20181150. doi: 10.1042/BSR20181150. Print 2018 Oct 31.

Abstract

Long non-coding RNAs (lncRNAs) have been involved in occurrence and progression of multiple cancers. In the present study, we investigated the role of lncRNA Gm15290 in the proliferation and invasion of non-small cell lung cancer (NSCLC) cells. First, we found that lncRNA Gm15290 was markedly up-regulated in tumor tissues from NSCLC patients and NSCLC cell lines, compared with adjacent normal tissues and normal lung cell line HBE respectively. Then, different concentrations of pcDNA-Gm15290 expression vector and Gm15290 siRNA were respectively transfected into A549 NSCLC cells. Our results showed that overexpression of Gm15290 significantly increased the proliferation and invasion of A549 cells and suppressed cell apoptosis. Knockdown of Gm15290 suppressed A549 cell proliferation and invasion and promoted cell apoptosis. Subsequently, we explored the underlying mechanism through which Gm15290 promoted cell proliferation and invasion. The output of RNA hybrid bioinformatic tool revealed that Gm15290 potentially interacted with tumor suppressor miR-615-5p which displayed an opposite expression pattern in the cell lines and a strong negative correlation with the levels of Gm15290 in NSCLC patients (r2 = 0.9677, P<0.0001). The results of RNA pull-down assays confirmed that Gm15290 directly bound with miR-615-5p Gm15290 negatively regulated the expression of miR-615-5p and increased the protein levels of miR-615-5p target genes, including IGF2, AKT2, and SHMT2 Moreover, miR-615-5p mimic could antagonize the promoting effect of Gm15290 on cell proliferation and invasion.

Keywords: RNA interaction; cell proliferation and invasion; lncRNA Gm15290; miR-615-5p; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glycine Hydroxymethyltransferase / genetics
  • Glycine Hydroxymethyltransferase / metabolism
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Antagomirs
  • IGF2 protein, human
  • MIRN615 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Insulin-Like Growth Factor II
  • Glycine Hydroxymethyltransferase
  • SHMT protein, human
  • AKT2 protein, human
  • Proto-Oncogene Proteins c-akt