Abstract
BackgroundRNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. Our previous studies suggested that RBM5 expression was negatively correlated with the expression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues. This study was aimed at determining whether RBM5 is able to regulate EGFR expression.MethodsBoth in vitro and in vivo studies were carried out to determine the effect of RBM5 on the expression of EGFR. Lentiviral vector-mediated RBM5 overexpression was employed in lung adenocarcinoma cell line A549. A549 xenograft mice were treated with recombinant RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Real-time quantitative polymerase chain reaction and Western blot were carried out to detect RBM5 and EGFR expression.ResultsBoth in vivo and in vitro studies indicated that the expression of EGFR mRNA and protein was decreased significantly in the RBM5 overexpression group compared to control groups as shown by real-time PCR and Western blot analysis. We identified that RBM5 overexpression inhibited EGFR expression both in A549 cells and in A549 xenograft mice model.ConclusionsOur study demonstrated that EGFR expression is regulated by RBM5 in lung adenocarcinomas cells either in a direct or indirect way, which might be meaningful with regards to target therapy in lung cancer.
Highlights
RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes
We identified that RBM5 overexpression inhibited epidermal growth factor receptor (EGFR) expression both in A549 cells and in A549 xenograft mice model
Our study demonstrated that EGFR expression is regulated by RBM5 in lung adenocarcinomas cells either in a direct or indirect way, which might be meaningful with regards to target therapy in lung cancer
Summary
RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. Our previous studies suggested that RBM5 expression was negatively correlated with the expression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues. Epidermal growth factor receptor (EGFR) ( known as HER-1 or Erb1) is a cell-surface receptor belonging to Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin. EGFR activation is associated with cell apoptosis, proliferation, angiogenesis, invasion, and metastasis, which plays an important role in carcinogenesis and tumor progression in human epithelial cancers, including NSCLC [4]. These actions are accomplished through activation of the RAS-RAF-MEK-ERK and PI3K-AKTmTOR pathways [5]. EGFR and PI3K initiate malignant neoplastic transformation via a combinatorial genetic network composed of other pathways, including the Tor, Myc, G1 Cyclins-Cdks, and Rb-E2F pathways [6], and drive cells through the restriction point of late G(1) into S phase [7]
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