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CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis.

ABSTRACT: CCL14 is a member of CC chemokines and its role in hepatocellular carcinoma (HCC) is still unknown. In this study, CCL14 expression were analyzed by tissue microarray (TMA) including 171 paired tumor and peritumor tissues of patients from Zhongshan Hospital of Fudan University. We found for the first time that CCL14 was downregulated in HCC tumor tissues compared with peritumor tissues (P?=?0.01). Meanwhile, CCL14 low expression in HCC tumor tissues is associated with a poor prognosis (P?=?0.035). CCL14 also displayed its predictive value in high differentiation (P?=?0.026), liver cirrhosis (P?=?0.003), and no tumor capsule (P?=?0.024) subgroups. The underlying mechanisms were further investigated in HCC cell lines by CCL14 overexpression and knock-down in vitro. We found overexpression of CCL14 suppressed proliferation and promoted apoptosis of HCC cells. Finally, the effect was confirmed by animal xenograft tumor models in vivo. The results shown overexpression of CCL14 lead to inhibiting the growth of tumor in nude mice. Interestingly, our data also implied that CCL14 played these effects by inhibiting the activation of Wnt/?-catenin pathway. These findings suggest CCL14 is a novel prognostic factor of HCC and serve as a tumor suppressor.

SUBMITTER: Zhu M

PROVIDER: S-EPMC6805940 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis.

Zhu Mengxuan M Xu Weiyue W Wei Chuanyuan C Huang Jing J Xu Jietian J Zhang Yuye Y Zhao Yan Y Chen Jie J Dong Shuangshuang S Liu Binbin B Liang Chunmin C

Cell death & disease 20191022 11

CCL14 is a member of CC chemokines and its role in hepatocellular carcinoma (HCC) is still unknown. In this study, CCL14 expression were analyzed by tissue microarray (TMA) including 171 paired tumor and peritumor tissues of patients from Zhongshan Hospital of Fudan University. We found for the first time that CCL14 was downregulated in HCC tumor tissues compared with peritumor tissues (P = 0.01). Meanwhile, CCL14 low expression in HCC tumor tissues is associated with a poor prognosis (P = 0.035 ...[more]

PMID: 31641099

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Project description:BackgroundRGS protein family members have recently became new potentially promising therapeutic targets in many cancers. However, as a key member of RGS family, RGS16 has seldom been studied in glioma. The present study was designed to investigate the prognostic value and biological function of RGS16 based on large-scale databases and functional assays in vitro.MethodsHere, we performed comprehensive analysis for the expression characteristic of RGS16 in Chinese Glioma Genome Atlas (CGGA) microarray database with 301 patients and validated in The Cancer Genome Atlas (TCGA) microarray and RNA sequencing database. Student's t-test, one-way ANOVA test and long-rank test were used to assess differences between groups. Kaplan-Meier survival, univariate and multivariate Cox analysis and ROC curve were used to estimate the survival distributions. Biological implication of abnormal expression of RGS16 in glioma was also explored. Functional analysis of RGS16 was performed in several glioblastoma (GBM) cell lines. R language and SPSS were used for statistical analysis and graphical work.ResultsWe found that the expression of RGS16 was positively related to the grade of glioma. High level of RGS16 commonly gathered in glioma of mesenchymal subtype and wild-type IDH1. Moreover, higher expression level of RGS16 was found to be significantly correlated with poor prognosis. The univariate and multivariate Cox regression analysis and ROC curve showed that RGS16 was an independent prognostic factor for glioma patients. Gene ontology analysis, gene set enrichment analysis, and gene set variation analysis suggested that the overexpression of RGS16 tightly related to cell proliferation, migration, epithelial-mesenchymal transition (EMT), immune and inflammatory response of glioma. Knockdown of RGS16 in glioma cell lines also showed that RGS16 promoted the malignant progress of glioma cell lines.ConclusionsRGS16 plays an important role in glioma progression and serves as an independent prognostic factor, especially in GBM patients.

Dataset Information

CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis.

Publications

CCL14 serves as a novel prognostic factor and tumor suppressor of HCC by modulating cell cycle and promoting apoptosis.

Similar Datasets

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