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

Liao, Susan; Chen, Hongyu; Liu, Min; Gan, Li; Li, Chuanfei; Zhang, Wenguang; Lv, Lin; Mei, Zhechuan

doi:10.18632/aging.102698

Cited by 56 publications

(40 citation statements)

References 34 publications

(37 reference statements)

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“…It is crucial for the maintenance of the stemness of murine mesenchymal stem cells [ 24 , 25 ]. AQP9 is downregulated in hepatocellular carcinoma but is elevated in many other cancers, including clear cell renal cell carcinoma, which suggests that it plays a complex role in cancer development [ 26 , 27 ]. A few bioinformatic studies have shown that COL8A1 is a hub gene associated with several cancers, but this requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma

Zhou

Yang

Mei

et al. 2021

BioMed Research International

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Background. Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis. Methods. mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40290) were selected. After all samples in each dataset were subjected to quality control using principal component analyses, the qualified samples were used for additional analyses. The genes that were significantly expressed in each dataset were intersected to identify the most significant of these. Gene functional enrichment analyses were performed on these genes, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. The protein–protein interaction network of selected genes was analyzed using the Search Tool for the Retrieval of Interacting Genes database. Significantly, differentially expressed genes were further verified with two RNA-seq datasets (GSE68799 and GSE12452), as well as in clinical samples. Results. In all, 34 (8 upregulated genes and 26 downregulated) genes were identified as significantly differentially expressed. The immune response and the regulation of cell proliferation were the most enriched biological GO terms. Using reverse transcription quantitative real-time PCR (RT-qPCR), the genes MMP1, AQP9, and TNFAIP6 were detected to be upregulated, and FAM3D, CR2, and LTF were downregulated in NPC tissue samples. Conclusion. This study provides information on the genes that may be involved in the development of NPC and suggests possible druggable targets and biomarkers for diagnosing and evaluating the prognosis of NPC.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma

Zhou

Yang

Mei

et al. 2021

BioMed Research International

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“…A recent study found that PCNA knockdown-HepG2 cells under hypoxia showed the induction of more epithelial-mesenchymal transition (EMT) process compared to the control [19]. PCNA and EMT-related markers were down-regulated following treatment with Wnt/β-catenin signaling inhibitor (XAV939) and the proliferative activity of HCC cells was significantly inhibited [20]. MutS homolog 6 (MSH6) is a member of the DNA mismatch repair MutS family.…”

Section: Discussionmentioning

confidence: 99%

Identification of a protein signature for predicting overall survival of hepatocellular carcinoma: a study based on data mining

Yang

2020

BMC Cancer

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Background: Hepatocellular carcinoma (HCC), is the fifth most common cancer in the world and the second most common cause of cancer-related deaths. Over 500,000 new HCC cases are diagnosed each year. Combining advanced genomic analysis with proteomic characterization not only has great potential in the discovery of useful biomarkers but also drives the development of new diagnostic methods. Methods: This study obtained proteomic data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) and validated in The Cancer Proteome Atlas (TCPA) and TCGA dataset to identify HCC biomarkers and the dysfunctional of proteogenomics. Results: The CPTAC database contained data for 159 patients diagnosed with Hepatitis-B related HCC and 422 differentially expressed proteins (112 upregulated and 310 downregulated proteins). Restricting our analysis to the intersection in survival-related proteins between CPTAC and TCPA database revealed four coverage survival-related proteins including PCNA, MSH6, CDK1, and ASNS. Conclusion: This study established a novel protein signature for HCC prognosis prediction using data retrieved from online databases. However, the signatures need to be verified using independent cohorts and functional experiments.

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“…AQP9 acts as a tumor suppressor in HCC invasion via the regulation of HIF-1α expression in the tumor hypoxic microenvironment. Furthermore, AQP9 overexpression was found to result in reactive oxygen species (ROS) accumulation, which inhibited β-catenin activity by attenuating the interaction of β-catenin with TCF4 while concurrently enhancing the association of β-catenin with FOXO3a, ultimately inhibiting liver cancer stem cells (LCSCs) (12,(14)(15)(16)(17); However, the prognostic value of AQP9 and the specific mechanism underlying its role in HCC remain to be further elucidated. Therefore, in this study, we conducted a bioinformatics analysis of AQP9 in liver cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Liver steatosis is characterized by ectopic accumulation of fat and altered glycerol uptake, and interestingly, AQP9 are dysregulated in liver steatosis mice (11)(12)(13). In humans, there is evidence to suggest that AQP9 inhibits the progression of HCC via the Wnt/β-catenin pathway (14), as well as epithelialto-mesenchymal transition (15) and the ROS-HIF-1α signaling pathway (16,17). However, the value of AQP9 in the diagnosis and prognosis of HCC as well as the changes in genes and pathways related to AQP9, immune infiltration levels and the reason for the decrease of AQP9 expression in HCC remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Low expression of AQP9 and its value in hepatocellular carcinoma

Gao¹,

Shen²,

Yao³

et al. 2021

Transl Cancer Res TCR

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Background: The mortality rate for liver cancer is high worldwide. The etiology of liver cancer has altered with the high incidence rate of non-alcoholic fatty liver disease (NAFLD) although effective vaccination strategies have been developed. Therefore, it is important to discover new biomarkers for diagnosis and prognosis. Aquaporin 9 (AQP9) has been reported in some cancers, especially in liver cancer, although its role in this malignancy remains to be clarified. In this study, we conducted a bioinformatics analysis to clarify the function of AQP9 in liver cancer.Methods: Immunohistochemistry, real-time qPCR, western blot analysis were applied to detect AQP9 expression in tissue samples or cells. Online databases were used to analyze the correlation of AQP9 expression and clinical factors. LinkedOmics and gene set enrichment analysis (GSEA) were used to analyze the functional network of AQP9 in hepatocellular carcinoma (HCC). Four authoritative databases were used to predict the candidate microRNAs that bind to AQP9. Finally, we used the Tumor Immune Estimation Resource (TIMER) to assess the correlation of AQP9 and immune cell infiltration in HCC.Results: All analysis were revealed AQP9 is significantly decreased in HCC tissues and cells. AQP9 was negatively correlated with different tumor stage, grade, and weight, as well as lymph node metastasis, sex, and histological subtypes. AQP9 can be used to predict the prognosis of HCC patients. GSEA revealed that AQP9 was significantly involved in most significant hallmark pathways. LinkedOmics was used to analyze the relationship of AQP9 with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Mechanistically, mir-23a-3p and mir-330-3p may downregulate AQP9 expression in HCC. AQP9 was found to be specifically correlated with immune cell infiltration and play a major role in the liver cancer microenvironment.Conclusions: In this study, we found that AQP9 was significantly decreased in HCC, with low AQP9 levels indicating a poor outcome. GSEA analysis and LinkedOmics revealed that AQP9 was significantly involved in the most significant hallmarks pathways. Mir-23a-3p and mir-330-3p may inhibit AQP9 expression in HCC. Our results also suggest that AQP9 is important in tumor immunity in the liver cancer.

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

Cited by 56 publications

References 34 publications

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma

Transcriptomic Analyses Reveal Gene Expression Profiles and Networks in Nasopharyngeal Carcinoma

Identification of a protein signature for predicting overall survival of hepatocellular carcinoma: a study based on data mining

Low expression of AQP9 and its value in hepatocellular carcinoma

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