A gene mutation in RNA‑binding protein 10 is associated with lung adenocarcinoma progression and poor prognosis

Abstract

RBM10 regulates the expression of various genes, which are often mutated in male lung adenocarcinoma. The present study confirmed the association of the RBM10 mutation at exon 10 with the clinicopathological data and prognosis of lung adenocarcinoma. The effect of mutant RBM10 on regulating lung cancer cell growth and invasion was investigated in vitro. Tissue specimens from 50 patients with lung adenocarcinoma were subjected to Sanger sequencing for RBM10 exon 10 mutations. Lung adenocarcinoma cells were transfected with pcDNA3.1 carrying wild type RBM10 cDNA or exon mutation cDNA for cell viability, apoptosis and invasion assays. RBM10 exon 10 mutations were identified in 11 out of 50 patients, with a high frequency in male patients [c.763 C>T, p.Arg241Cys for 33.3% (10/30)] and were significantly associated with the American Joint Committee on Cancer stage (P=0.005), lymph node metastasis (P=0.019) and shorter 5-year survival rate compared with the wild type RBM10 (36.4% vs. 46.5%; P=0.019). Multivariate analysis revealed that RBM10 exon 10 mutation was an independent prognostic factor (HR=3.787; P=0.033). RBM10 exon 10 mutation at c.763 C>T significantly promoted tumor cell proliferation and invasion capacity, whereas wild type RBM10 inhibited tumor cell invasion in vitro. In conclusion, RBM 10 mutation at exon 10 (c.763 C>T) occurs frequently and is an independent prognostic predictor in lung adenocarcinoma.

RNA-binding proteins in human genetic disease

“…In addition to TARP syndrome, somatic mutations in the RBM10 gene occur in numerous cancers, including lung adenocarcinoma [84][85][86][87] , colorectal cancer 88 , pancreatic cancer 89 and bladder cancer 90 . Consistent with context-specific functions of RBPs in cancer, RBM10 can function as a tumour suppressor or an oncogene [91][92][93] , possibly linked to expression of alternatively spliced variants and cross-regulatory feedback loops with the related protein RBM5 (ref.…”

RBM10 Regulates Tumor Apoptosis, Proliferation, and Metastasis

“…By binding to small nuclear ribonucleoprotein (snRNPs) and cleavage sites of pre-mRNA substrates, RBM10 can synergistically remove introns and increase exon jumping events by more than 74% ( 23 , 24 ). The change in RBM10 abundance and activity can lead to changes in some gene splicing patterns and the occurrence of many diseases, such as LUAD ( 25 ).…”

“…The studies reviewed here have shown that deletion or mutation of RBM10 is associated with the occurrence and poor prognosis of human cancers, including lung and pancreatic cancer ( 6 , 34 ). For example, RBM10 mutation is significantly associated with the American Joint Committee on Cancer (AJCC) stage diagnostics, lymph node metastasis, and male patients, but not with smoking, age, tumor size, or differentiation ( 25 ). Mutations in exon 10 of RBM10 can significantly promote the proliferation and invasion of tumor cells, and the 5-year survival rate of patients with these mutations was significantly lower than that observed in healthy individuals (36.4 vs .…”

“…Mutations in exon 10 of RBM10 can significantly promote the proliferation and invasion of tumor cells, and the 5-year survival rate of patients with these mutations was significantly lower than that observed in healthy individuals (36.4 vs . 46.5% of RBM 10 wild type; χ2 = 5.466, P = 0.019) ( 25 ). However, some RBM10 mutations are also related to the improvement in survival rate ( 6 ), suggesting that our understanding of the specific pathogenic patterns of RBM10 mutagenesis is still limited.…”

“…For example, RBM10 mutation is significantly associated with the American Joint Committee on Cancer (AJCC) stage diagnostics, lymph node metastasis, and male patients, but not with smoking, age, tumor size, or differentiation (25). Mutations in exon 10 of RBM10 can significantly promote the proliferation and invasion of tumor cells, and the 5-year survival rate of patients with these mutations was significantly lower than that observed in healthy individuals (36.4 vs. 46.5% of RBM 10 wild type; c2 = 5.466, P = 0.019) (25). However, some RBM10 mutations are also related to the improvement in survival rate (6), suggesting that our understanding of the specific pathogenic patterns of RBM10 mutagenesis is still limited.…”