Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells

Tumour Biol. 2017 Mar;39(3):1010428317691740. doi: 10.1177/1010428317691740.

Abstract

This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression.

Keywords: RNA-binding motif 10; complementary DNA microarray; lung adenocarcinoma; tumor suppressor gene.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics

Substances

  • RBM10 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins