下调和上调
肝细胞癌
癌症研究
细胞周期蛋白D1
细胞凋亡
酪氨酸磷酸化
细胞生长
生物
细胞周期
分子生物学
激酶
细胞生物学
生物化学
基因
作者
Xiang‐Nan Yu,Hongying Guo,Taotao Liu,Guangcong Zhang,Hairong Zhu,Xuan Shi,Guangqi Song,Xuemei Jiang,Xiaoxi Huang,Shu‐Qiang Weng,Ling Dong,Xizhong Shen,Yangqing Huang,Ji‐Min Zhu
摘要
Abstract Background Calcium‐binding tyrosine phosphorylation‐regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR‐a/b (combined CABYR‐a and CABYR‐b), in HCC remain to be established. Methods CABYR‐a/b expression was detected in HCC tissues and cell lines by quantitative real‐time polymerase chain reaction and Western blot analysis. The correlation of CABYR‐a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR‐a/b were also investigated using molecular biology approaches. Results The present research found that CABYR‐a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR‐a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR‐a/b level had poorer overall survival (OS) and disease‐free survival (DFS) than those with reduced CABYR‐a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR‐a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR‐a/b downregulation suppressed cell proliferation and induced G1‐phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B‐cell lymphoma 2 (Bcl‐2) and increasing Bcl‐2‐associated death promoter. Conclusion Our research indicates that CABYR‐a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.
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