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

Shi, Chao; Huang, Dengliang; Lü, Nonghua; Chen, Dan; Zhang, Min-Hong; Yan, Yizhong; Deng, Libin; Lu, Quqin; Lu, Hua; Luo, Shuhong

doi:10.18632/oncotarget.8441

Cited by 69 publications

(86 citation statements)

References 42 publications

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“…KIF20A is a member of the KIF family, which has been reported to be upregulated in pancreatic cancer,29 breast cancer,14 and hepatocellular cancer 30. In the current study, we investigated the expression of KIF20A protein in gliomas using IHC and found that the expression of KIF20A is positively correlated with Ki67 expression, suggesting that KIF20A may participate in the proliferation of gliomas.…”

Section: Discussionmentioning

confidence: 64%

Positive expression of KIF20A indicates poor prognosis of glioma patients

Duan

Huang

2016

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Glioma patients have a poor overall survival; however, patients can show distinct clinical outcomes due to the high heterogeneity of the tumor, which may be indicated by certain clinicobiological parameters. Kinesin family member 20A (KIF20A), which participates in cytokinesis and intracellular transportation, has been recently reported to be upregulated in pancreatic cancer, breast cancer, and bladder cancer. In the current study, we investigated the expression of KIF20A in gliomas and its significance in predicting the prognosis after surgery. We found that KIF20A positive expression in glioma tissues correlated significantly with Ki67 protein expression and advanced World Health Organization grade. Univariate and multivariate analysis revealed that KIF20A can act as an independent prognostic factor for predicting the overall survival of glioma patients. Moreover, we demonstrated that KIF20A can positively regulate the expression of Ki67 in glioma cell lines. Correspondingly, overexpression of KIF20A can promote cell proliferation and invasion, whereas knockdown of KIF20A can inhibit cell viability and invasion capacity. In vitro study also showed that under the treatment of plumbagin, an anticancer drug, KIF20A expression decreased in a dose-dependent manner. In addition, the overexpression of KIF20A can also increase the drug resistance toward plumbagin, which provided the possibility that KIF20A may contribute to the chemotherapy resistance of gliomas.

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Section: Discussionmentioning

confidence: 64%

Positive expression of KIF20A indicates poor prognosis of glioma patients

Duan

Huang

2016

OTT

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“…Knockdown of KIF20A could significantly inhibit the growth of HCC cells in vitro and also suppress the growth of HCC xenografts in vivo . Based on the survival data of 210 HCC patients from China, this study also showed elevated KIF20A expression was associated with poor survivals . Therefore, KIF20A might be a promising prognostic indicator in HCC.…”

Section: Introductionmentioning

confidence: 69%

Aberrant KIF20A expression might independently predict poor overall survival and recurrence‐free survival of hepatocellular carcinoma

Huang

Chen

et al. 2018

IUBMB Life

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Kinesin family member 20A (KIF20A) is an essential regulator of cytokinesis. In this study, by performing a retrospective study based on data from the Cancer Genome Atlas (TCGA)-Liver and Hepatocellular Carcinoma (LIHC) cohort, we tried to assess the independent prognostic value of KIF20A in terms of overall survival (OS) and recurrence-free survival (RFS). Results showed that normal liver tissues had very low KIF20A expression compared with normal tissues in other cohorts in TCGA. However, the primary HCC tissues (N = 371) had significantly elevated KIF20A expression than normal liver tissues (N = 50). Immunohistochemistry (IHC) data showed that normal hepatocytes had weak KIF20A staining. In comparison, some HCC tissues had medium and strong KIF20A expression, with nuclear-enhanced staining. By grouping patients with primary HCC (N = 365) into high and low KIF20A expression groups, we found that the high expression group had a substantially higher proportion of high-grade tumors (G3/G4) (34/65, 52.3% vs. 96/295, 32.5%, P = 0.0027), advanced tumors (stage III/IV) (28/61, 45.9% vs. 59/280, 21.1%, P < 0.0001) and death (44/67, 65.7% vs. 86/298, 28.9%, P < 0.0001) compared with the low expression group. Kaplan-Meier curves of OS and RFS indicated that high KIF20A expression was associated with worse survival outcomes. Subgroup analysis confirmed the associations in G1/G2, G3/G4 tumors and in early and advanced stages. Following univariate and multivariate analysis revealed that KIF20A expression was an independent prognostic indicator for poor OS (HR: 1.304, 95%CI: 1.157-1.469, P < 0.001) and RFS (HR: 1.144, 95%CI: 1.028-1.272, P < 0.001). Based on these findings, we infer that KIF20A was aberrantly expressed in HCC tissues and its expression might independently predict poor OS and RFS. © 2018 IUBMB Life, 70(4):328-335, 2018.

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“…6C). In addition, the protein degradation of Gli2 was accelerated significantly in Nek2A over-expressed HepG2 cells which is also a Hh-responsive cell line [30] (Fig. 6D).…”

Section: Nek2a Impairs Gli2 Activitymentioning

confidence: 88%

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

Cited by 69 publications

References 42 publications

Positive expression of KIF20A indicates poor prognosis of glioma patients

Positive expression of KIF20A indicates poor prognosis of glioma patients

Aberrant KIF20A expression might independently predict poor overall survival and recurrence‐free survival of hepatocellular carcinoma

Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism

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