CFDP1 promotes hepatocellular carcinoma progression through activating NEDD4/PTEN/PI3K/AKT signaling pathway

被引:14
作者
Zhou, Yan [1 ]
Qiu, Jiannan [2 ,3 ]
Liu, Siyuan [1 ]
Wang, Peng [2 ,3 ]
Ma, Ding [2 ,3 ]
Zhang, Guang [1 ,2 ,3 ,4 ]
Cao, Yin [1 ,2 ,3 ,4 ]
Hu, Lili [1 ]
Wang, Zhongxia [1 ,2 ,3 ,4 ]
Wu, Junhua [3 ,4 ]
Jiang, Chunping [1 ,2 ,3 ,4 ]
机构
[1] Nanjing Med Univ, Drum Tower Clin Coll, Dept Hepatobiliary Surg, 321 Zhong Shang Rd, Nanjing 210000, Peoples R China
[2] Nanjing Univ, Med Sch, Affiliated Drum Tover Hosp, Dept Hepatobiliary Surg, Nanjing, Peoples R China
[3] Nanjing Univ, Med Sch, Natl Inst Healthcare Data Sci, Jiangsu Key Lab Mol Med, 22 Han Kou Rd, Nanjing 210000, Peoples R China
[4] Jinan Microecol Biomed Shandong Lab, Shounuo City Light West Block, Jinan, Peoples R China
基金
中国国家自然科学基金;
关键词
CFDP1; hepatocellular carcinoma; NEDD4; PI3K; AKT signaling pathway; UBIQUITIN LIGASES; GENE-EXPRESSION; NEDD4;
D O I
10.1002/cam4.4919
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background and Aims It is being increasingly reported that the Cranio Facial Development Protein 1 (CFDP1) plays a significant role in the onset and progression of tumors. Nonetheless, the underlying mechanisms associated with CFDP1 that contribute to hepatocellular carcinoma (HCC) and the specific biological role of CFDP1 remain vague. Methods The Gene Expression Omnibus (GEO) database was analyzed to obtain the gene expression profiles as well as the matching clinical data of HCC patients. The gene co-expression network was developed by means of weighted gene co-expression network analysis (WGCNA) to screen for possible biomarkers that could be used for the purpose of predicting prognosis. The Cancer Genome Atlas (TCGA) and Gene Expression Profile Interaction Analysis (GEPIA) databases were used to assess the relationship between survival and expression. In addition, we identified the underlying mechanism associated with CFDP1 by analyzing the KEGG pathway database, applying the GSEA and GeneCards analysis method. We performed a sequence of experiments (in vivo and in vitro) for the purpose of investigating the specific function of CFDP1 in liver cancer. Results The obtained results revealed high expression of CFDP1 in HCC tissues and cell lines. A positive correlation between the overexpression of CFDP1 and the adverse clinicopathological features was observed. Moreover, we observed that the low recurrence-free survival and overall survival were associated with CFDP1 overexpression. In addition, GeneCards and GSEA analysis showed that CFDP1 may interact with NEDD4 and participate in PTEN regulation. Meanwhile, CFDP1 can promote the malignant development of liver cancer in vivo and in vitro. The western blotting technique was also employed so as to examine the samples, and the findings demonstrated that CFDP1 enhanced the malignancy of HCC via the NEDD4-mediated PTEN/PI3K/AKT pathway. Conclusion We highlighted that CFDP1 played an oncogenic role in HCC and was identified as a possible clinical prognostic factor and a potential novel therapeutic target for HCC.
引用
收藏
页码:425 / 444
页数:20
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