Elevation of MAP17 enhances the malignant behavior of cells via the Akt/mTOR pathway in hepatocellular carcinoma
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Xinhuang Chen1,*, Yan Liao2,*, Yaqun Yu3, Pengpeng Zhu1, Jun Li1, Liling Qin1, Weijia Liao1,4 and Zhaoquan Huang4,5
1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China
2Disease Prevention and Control Center of Guilin, Guilin, Guangxi, P.R. China
3Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China
4Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, Guangxi, P.R. China
5Department of Pathology, Guilin Medical University, Guilin, Guangxi, P.R. China
*These authors have contributed equally to this work
Weijia Liao, email: [email protected]
Zhaoquan Huang, email: [email protected]
Keywords: hepatocellular carcinoma, MAP17, progression, Akt/mTOR, prognosis
Received: December 08, 2016 Accepted: August 28, 2017 Published: October 04, 2017
MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels. High MAP17 expression was positively correlated with gender, distant metastasis, early recurrence (≤ 2 year), and serum alpha-fetoprotein (all p < 0.05). Kaplan-Meier analysis showed that the DFS (p = 0.004) and OS (p = 0.013) in HCC patients with elevated expression of MAP17 were much worse than that in the low expression subgroup. High level of MAP17 was also significantly associated with a high probability of HCC early recurrence after surgical resection (p = 0.005). Cox regression analysis indicated MAP17 was an independent prognostic factor for DFS (HR, 1.710; 95% CI, 1.156-2.449, p = 0.012) and OS (HR, 1.743; 95% CI, 1.152-2.639, p = 0.009) in HCC. Silencing MAP17 significantly inhibited the proliferation, invasion and migration of HCC cells in vitro, and decreased the expression levels of Akt, p-Akt (Ser473), mTOR, p-mTOR (Ser2448) and MMP-9. Suggesting MAP17 was a novel diagnostic and prognostic biomarker for HCC patients and promoted HCC cell proliferation, invasion and migration via the Akt/mTOR pathway.
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