The tumor suppressor gene RBM5 inhibits lung adenocarcinoma cell growth and induces apoptosis

Abstract

BackgroundThe loss of tumor suppressor gene (TSG) function is a critical step in the pathogenesis of human lung cancer. RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 demonstrated tumor suppressor activity. However, the role of RBM5 played in the occurrence and development of lung cancer is still not well understood.MethodPaired non-tumor and tumor tissues were obtained from 30 adenocarcinomas. The expression of RBM5 mRNA and protein was examined by RT-PCR and Western blot. A549 cell line was used to determine the apoptotic function of RBM5 in vitro. A549 cells were transiently transfected with pcDNA3.1-RBM5. AnnexinV analysis was performed by flow cytometry. Expression of Bcl-2, cleaved caspase-3, caspase-9 and PAPP proteins in A549 lung cancer cells and the A549 xenograft BALB/c nude mice model was determined by Western blot. Tumor suppressor activity of RBM5 was also examined in the A549 xenograft model treated with pcDNA3.1-RBM5 plasmid carried by attenuated Salmonella typhi Ty21a.ResultThe expression of RBM5 mRNA and protein was decreased significantly in adenocarcinoma tissues compared to that in the non-tumor tissues. In addition, as compared to the vector control, a significant growth inhibition of A549 lung cancer cells was observed when transfected with pcDNA3.1-RBM5 as determined by cell proliferation assay. We also found that overexpression of RBM5 induced both early and late apoptosis in A549 cells using AnnexinV/PI staining as determined by flow cytometry. Furthermore, the expression of Bcl-2 protein was decreased, whereas the expression of cleaved caspase-3, caspase-9 and PARP proteins was significantly increased in the RBM5 transfected cells; similarly, expression of decreased Bcl-2 and increased cleaved caspase-3 proteins was also examined in the A549 xenograft model. More importantly, we showed that accumulative and stable overexpression of RBM5 in the A549 xenograft BALB/c nude mice model significantly inhibited the tumor growth rate in vivo as compared to that in the control.ConclusionOur study demonstrates that RBM5 can inhibit the growth of lung cancer cells and induce apoptosis both in vitro and in vivo, which suggests that RBM5 might be used as a potential biomarker or target for lung cancer diagnosis and chemotherapy. Moreover, we propose a novel animal model set up in BALB/c nude mice treated with attenuated Salmonella as a vector carrying plasmids to determine RBM5 function in vivo.

Differential expression of RBM5 and KRAS in pancreatic ductal adenocarcinoma and their association with clinicopathological features

“…Additionally, underexpression of RBM5 had a close association with unfavorable clinicopathological features, including lymph node metastasis, distant metastasis, advanced UICC stage and presence of nerve and venous invasion, suggesting its potential role in tumor invasion and progression. Several studies have showed that RBM5 is differentially expressed in human cancers and is involved in tumorigenesis (15–18). Oh et al (19) found that the tumor suppressor RBM5/H37 alters the expression of genes involved in metastasis, suggesting that a loss of RBM5 expression may increase the metastatic potential of tumors.…”

The human RBPome: From genes and proteins to human disease

“…Of all the disorders annotated for human genes in malacards, 165 were found to be highly enriched for RBPs (p<1e-05, FDR<1% and number of annotated RBPs >10) which included all major types of cancers -breast, lung, prostate and liver as well as neurodegenerative diseasesParkinson's disease and down syndrome ( Figure 5A). For example, genes like ELAV1, which regulate mRNA stability are known to contribute to breast cancer [65], RBM5, a tumor suppressor gene is known to control cell growth in lung cancer [66], UPF1, subunit of the post splicing multi protein complex is shown to be dysregulated in prostate cancer [67]. RBPs that are known to be dysregulated in neurodegenerative diseases include members of the NOVA family [68], QKI, a candidate gene for schizophrenia [69] and ELAVL4, an important player in parkinson's disease [70].…”

RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways

“…In regards to lung cancer specifically, some functional work regarding RBM5 has been performed using a lung adenocarcinoma cell line (A549), which showed that increased RBM5 expression correlated with (a) G 1 cell cycle arrest (Network, 2014; Shao et al, 2012), and (b) increased apoptosis (Oh et al, 2006; Shao et al, 2012). No functional work, however, has been undertaken for RBM5 in SCLC.…”