title: Aberrantly activated Gli2-KIF20A axis is crucial for growth of hepatocellular carcinoma and predicts poor prognosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Dengliang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Nonghua
authors.initials: N
authors.lastname: Lu
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Minhong
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Yehong
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Quqin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.affiliation: Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000075746:Zinc Finger Protein Gli2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C082593:GLI2 protein, human; C410089:KIF20A protein, human; D009687:Nuclear Proteins; D000075746:Zinc Finger Protein Gli2; D016547:Kinesins
keywords: Forkhead box M1; glioma-associated oncogene 2; hepatocellular carcinoma; kinesin family member 20A; transcriptional regulation