Increased expression of RBMS3 predicts a favorable prognosis in human gallbladder carcinoma

Wu,Youliang; Meng,Delong; You,Yexiang; Sun,Ruochuan; Yan,Qiang; Bao,Junjun; Sun,Yanjun; Yun,Dapeng; Li,Yongxiang; Sun,Dengqun

doi:10.3892/or.2020.7594

Increased expression of RBMS3 predicts a favorable prognosis in human gallbladder carcinoma

Authors:
- Youliang Wu
- Delong Meng
- Yexiang You
- Ruochuan Sun
- Qiang Yan
- Junjun Bao
- Yanjun Sun
- Dapeng Yun
- Yongxiang Li
- Dengqun Sun
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, Anhui 230041, P.R. China, Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Published online on: April 23, 2020 https://doi.org/10.3892/or.2020.7594
Pages: 55-68
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple regions in the short arm of chromosome 3 are frequently deleted in a variety of solid tumors including gallbladder carcinoma (GBC). RNA binding motif, single‑stranded interacting protein 3 (RBMS3), a tumor suppressor gene (TSG), is located in this region. However, the role of RBMS3 in GBC remains unclear. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to evaluate the mRNA and protein expression levels of RBMS3 in 41 fresh frozen GBC tissues and paired normal tissues. An immunohistochemical assay was performed on a tissue microarray (TMA, consisting of 125 cases GBC and 47 normal controls). Microvessel density (MVD) counts were determined using CD34 immunohistochemical staining. Moreover, univariate and multivariate analyses were performed to determine the correlations between RBMS3 expression, MVD and patient prognosis. Cellular functions including proliferation, clonogenicity and apoptosis, were assessed to further identify in vitro roles of RBMS3. It was revealed that both mRNA and protein expression levels of RBMS3 were significantly lower in GBC tissues than in normal controls. Multivariate Cox regression analyses demonstrated cytoplasmic RBMS3 expression as an independent prognostic factor correlated with GBC angiogenesis, histopathological differentiation and TNM stage. Kaplan‑Meier curves revealed that patients with lower cytoplasmic RBMS3 levels had a significantly worse OS than patients with higher cytoplasmic RBMS3 expression. Additionally, ectopic expression of RBMS3 markedly suppressed GBC cell proliferation and clonogenicity and promoted apoptosis in vitro. These findings indicated the potential of cytoplasmic RBMS3 as a tumor prognostic biomarker and a promising therapeutic target for GBC.

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