Increased α-Tubulin1b Expression Indicates Poor Prognosis and Resistance to Chemotherapy in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. It is important to understand molecular mechanisms of HCC progression and to develop clinically useful biomarkers for the disease. We aimed to investigate the possible involvement of α-tubulin1b (TUBA1B) in HCC pathology. Tissue specimens were obtained from 114 HCC patients during hepatectomy. Immunohistochemistry and western blot analysis were used to detect TUBA1B expression in HCC tissues and cell lines. TUBA1B was knocked down in HCC cells by siRNA transfection. CCK-8 assay and flow cytometry were applied to determine cell proliferation and cell cycle progression, respectively. The efficacy of paclitaxel chemotherapy was evaluated by plate colony formation assay. TUBA1B was higher expressed in HCC tumor tissues than in adjacent nontumor tissues. TUBA1B and Ki-67 expressions were positively related to each other, and both their expressions were significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that TUBA1B was a significant predictor for overall survival of HCC patients. TUBA1B expression was increased in HCC cells during the G1- to S-phase transition. TUBA1B knockout in HCC cells inhibited cell proliferation, and attenuated resistance to paclitaxel. Our results indicated that TUBA1B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increased TUBA1B expression was associated with poor overall survival and resistance to paclitaxel of HCC patients.