Immature colon carcinoma transcript-1 promotes cell growth of hepatocellular carcinoma via facilitating cell cycle progression and apoptosis resistance

Chang,Weiping; Yu,Zhaoxiang; Tian,Ming; Lin,Xiaobo

doi:10.3892/or.2017.6046

Immature colon carcinoma transcript-1 promotes cell growth of hepatocellular carcinoma via facilitating cell cycle progression and apoptosis resistance

Authors:
- Weiping Chang
- Zhaoxiang Yu
- Ming Tian
- Xiaobo Lin
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China
Published online on: October 19, 2017 https://doi.org/10.3892/or.2017.6046
Pages: 3489-3496

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Abstract

Immature colon carcinoma transcript-1 (ICT1) is a newly identified oncogene, which regulates proliferation, cell cycle progression and apoptosis of cancer cells. However, the clinical significance, biological function and underlying mechanisms of ICT1 in hepatocellular carcinoma (HCC) remain poorly known. In the present study, we showed that the expression of ICT1 in HCC tissues were notably overexpressed compared to corresponding non-tumor tissues. Accordingly, the relative levels of ICT1 were upregulated in HCC cell lines compared with LO2 cells. The positive expression of ICT1 was correlated with large tumor size and advanced TNM tumor stage. Kaplan-Meier plots indicated that ICT1-positive expression in HCC patients showed a prominent shorter survival. In addition, ICT1 knockdown inhibited proliferation and cell cycle progression, and induced apoptosis in HepG2 cells. While, ICT1 overexpression showed opposite effects on these cellular processes of Hep3B cells. In vivo experiments demonstrated that ICT1 deficiency reduced the growth of subcutaneous HCC in nude mice. Notably, ICT1 knockdown reduced the levels of CDK1, cyclin B1 and Bcl-2 and increased the expression of Bax in HepG2 cells. ICT1 overexpression resulted in upregulation of CDK1, cyclin B1 and Bcl-2, and downregulation of Bax in Hep3B cells. Furthermore, microRNA-134 (miR-134) was recognized as a direct upstream regulator and inversely modulated ICT1 abundance in HCC cells. Altogether, our data support that miR-134 regulation of ICT1 facilitates malignant phenotype of HCC cells probably via cell cycle and apoptosis-associated proteins including CDK1, cyclin B1, Bcl-2 and Bax.

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