Oncotarget

Research Papers:

Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B

Minghua Hu, Mingwei Wang, Huihong Lu, Xiaoming Wang, Xiaoshan Fang, Jinguo Wang, Chenyang Ma, Xiaobing Chen and Hongping Xia _

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Oncotarget. 2016; 7:43419-43431. https://doi.org/10.18632/oncotarget.9728

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Abstract

Minghua Hu1,*, Mingwei Wang2,*, Huihong Lu4,*, Xiaoming Wang1, Xiaoshan Fang1, Jinguo Wang1, Chenyang Ma1, Xiaobing Chen3, Hongping Xia1

1Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China

2Division of Cardiovascular Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China

3Department of Oncology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, China

4Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China

*These authors contributed equally to this work

Correspondence to:

Hongping Xia, email: xiahp82@gmail.com

Xiaobing Chen, email: 2290773710@qq.com

Keywords: miR-1258, liver cancer, recurrence, stemness, CKS1B

Received: March 14, 2016     Accepted: May 05, 2016     Published: May 30, 2016

ABSTRACT

Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients’ survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.


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