Dataset Information

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/?-catenin pathway.

ABSTRACT: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide, and it is the second leading cause of cancer-related mortality. Aquaporin 9 (AQP9) is an essential aquaporin in the liver and located in the basolateral membrane of hepatocytes, but its roles on HCC has not been completely elucidated. This study investigated the regulatory functions of AQP9 in the pathogenesis of HCC. The expression levels of AQP9 were significantly down-regulated in HCC tissues and cells, which was also correlated with tumor size and number, TNM stage, five-year survival rate, lymphatic and distal metastasis within the patients. Furthermore, overexpressed AQP9 suppressed the proliferation, migration and invasion of HCC cells. The levels of PCNA, E-cad, N-cad, ?-SMA, DVL2, GSK-3?, cyclinD1 and ?-catenin in HCC cells were reduced by overexpressed AQP9, while cell apoptosis was remarkably enhanced. Additionally, following the treatment with Wnt/?-catenin signaling inhibitor (XAV939), the proliferative activity of HCC cells was significantly inhibited; PCNA and EMT-related markers were down-regulated; migration and invasion of cells were notably suppressed; cell apoptotic rate was decreased. Vice versa, after the cells were treated with Wnt/?-catenin inducer (SKL2001), the effects caused by overexpressed AQP9 were abrogated. In vivo studies indicated that tumor volume and weight were remarkably decreased in AQP9 overexpression group, where the levels of Wnt/?-catenin signaling- and EMT-associated molecules were also reduced. Taken together, our results suggested that overexpressed AQP9 could inhibit growth and metastasis of HCC cells via Wnt/?-catenin pathway. AQP9 may be a promising therapeutic target for the treatment of patients with HCC.

SUBMITTER: Liao S

PROVIDER: S-EPMC7053619 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/β-catenin pathway.

Liao Shengtao S Chen Hongyu H Liu Min M Gan Li L Li Chuanfei C Zhang Wenguang W Lv Lin L Mei Zhechuan Z

Aging 20200122 2

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide, and it is the second leading cause of cancer-related mortality. Aquaporin 9 (AQP9) is an essential aquaporin in the liver and located in the basolateral membrane of hepatocytes, but its roles on HCC has not been completely elucidated. This study investigated the regulatory functions of AQP9 in the pathogenesis of HCC. The expression levels of AQP9 were significantly down-regulated in HCC tissues and cells, which wa ...[more]

PMID: 31969493

Similar Datasets

Project description:BackgroundLung cancer is the most common cancer in the world and is the main cause of cancer-related death. Revealing the potential mechanism of malignant characteristics of lung cancer is urgent for treating this disease effectively. Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. The role of ZNF671 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of this study was to investigate the function and mechanism of ZNF671 in NSCLC.MethodsZNF671 expression in NSCLC cells and tissues were detected by Real-Time PCR, Western blot and TCGA databases. Then, we evaluated the prognostic value of ZNF671 expression in NSCLC using the Kaplan-Meier plotter (KM plotter) and TCGA databases. Moreover, the function of ZNF671 in the proliferation and metastasis of lung cancer was investigated by MTT assay, colony formation assay, in vivo experiment, EdU assay, wound healing assay, transwell assay, and 3D culture assay. Luciferase reporter and subcellular fractionation assays were performed to determine the underlying mechanism of ZNF671-mediated proliferation and metastasis of NSCLC.ResultsZNF671 expression was significantly reduced in both NSCLC cell lines and clinical specimens compared to that in normal controls. The survival analysis results indicated that the downregulation of ZNF671 significantly correlates with poor prognosis and predicts a shorter overall survival and post-progression survival among NSCLC patients. Ectopic overexpression of ZNF671 dramatically restrains, whereas silencing ZNF671 enhanced, cell proliferation and metastasis of NSCLC. Mechanically, gene set enrichment analysis (GSEA) showed that the expression of ZNF671 was significantly correlated with Wnt/β-catenin signaling. Simultaneously, our results confirm that the overexpression of ZNF671 inhibits cell cycle progression and metastasis by weakening the Wnt/β-catenin pathway, and then downregulating the expression of downstream target genes CyclinD1 and MMP9.ConclusionThis study found that the overexpression of ZNF671 restrains the proliferation and metastasis of lung cancer through inhibiting Wnt/β-catenin signaling pathway. Furthermore, our current results provide important insights into ZNF671 as an excellent predictive biomarker for NSCLC, thus providing a novel perspective for the treatment of NSCLC.

Dataset Information

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/?-catenin pathway.

Publications

Aquaporin 9 inhibits growth and metastasis of hepatocellular carcinoma cells via Wnt/β-catenin pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets