Oncotarget

Research Papers:

Aberrantly activated Gli2-KIF20A axis is crucial for growth of hepatocellular carcinoma and predicts poor prognosis

Chao Shi, Dengliang Huang, Nonghua Lu, Dan Chen, Minhong Zhang, Yehong Yan, Libin Deng, Quqin Lu, Hua Lu and Shiwen Luo _

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Oncotarget. 2016; 7:26206-26219. https://doi.org/10.18632/oncotarget.8441

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Abstract

Chao Shi1, Dengliang Huang1, Nonghua Lu2, Dan Chen1, Minhong Zhang1, Yehong Yan3, Libin Deng4, Quqin Lu5, Hua Lu6, Shiwen Luo1

1Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

2Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

3Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

4Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, China

5Department of Epidemiology and Biostatistics, School of Public Health, Nanchang University, Nanchang, Jiangxi, China

6Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA

Correspondence to:

Shiwen Luo, email: [email protected]

Keywords: glioma-associated oncogene 2, Forkhead box M1, kinesin family member 20A, transcriptional regulation, hepatocellular carcinoma

Received: January 29, 2016     Accepted: March 14, 2016     Published: March 28, 2016

ABSTRACT

Glioma-associated oncogene 2 (Gli2), a primary transcriptional regulator of Hedgehog (Hh) signaling, is essential for hepatocellular carcinoma (HCC) growth and survival. However, the underlying molecular mechanism and crucial downstream targets of Gli2 in human HCC are not fully understood. Here, we report the identification of kinesin family member 20A (KIF20A) as a novel downstream target of Gli2, which is important for HCC proliferation and tumor growth. Inhibition of Hh signaling leads to a remarkable decrease of KIF20A expression in HCC cells, whereas overexpression of Gli2 elevates KIF20A expression by activating Forkhead Box M1 (FoxM1)-MMB complex-mediated transcription of this kinesin gene. Gli2-induced HCC cell growth requires enhanced expression of KIF20A, and knockdown of Gli2 or KIF20A represses the proliferation of HCC cells in vitro and in vivo. Correlated with these results, analyses of clinical HCC samples show that Gli2, FoxM1 and KIF20A are highly elevated in primary HCC samples and represent significant risk factors for HCC recurrence and survival. Conclusion: KIF20A is an important downstream target gene of Hh signaling. And, the Gli2-KIF20A axis is essential for the proliferation and growth of human HCC cells. Our study also suggests Gli2-KIF20A axis as a potential target for future therapeutic intervention and as an independent prognostic biomarker for HCC.


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