C -reactive protein promotes tumor progression in Hepatocellular Carcinom by 1 interacting with Ephrin type B receptor 3

Abstract C-reactive protein (CRP), an acute phase protein, has been increasingly implicated in various tumors, and the role of CRP is positively correlated with invasion and metastasis in hepatocellular carcinoma cells. However, the mechanism of CRP affecting HCC progression remains poorly investigated. The present study investigated the role of CRP in HCC and the underlying mechanisms. We first found that CRP was significantly upregulated in HCC tissues and HCC cells, the expression level correlated with the metastatic ability of HCC cells. Knockdown of CRP significantly suppresses migration and invasion capacity in HCC cells. Through a proteomic analysis of CRP co-immunoprecipitation complexes, the Eph receptor B3 was identified as a new CRP interactor. Then we found that the expression and functions of EphB3 were consistent with CRP in HCC. In addition, co-immunoprecipitation and immunofluorescence assays suggested that EphB3 was able to interact with MAPK/ERK to activate MAPK/ERK signaling pathways. Furthermore, we showed that CRP can induce the phosphorylation of MAPK/ERK by binding EphB3. Our findings showed that CRP increased HCC cells migration and invasion by binding EphB3 to activate MAPK/ERK signaling pathways. It suggested that CRP may become a prognostic factor and a potential therapeutic target for liver cancer.

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C-Reactive Protein Promotes Tumor Progression in Hepatocellular Carcinom by Interacting with Ephrin Type-B Receptor 3

10.21203/rs.3.rs-970664/v1 ◽

2021 ◽

Author(s):

Sha She ◽

Min Yang ◽

Shi Ying Li ◽

Huai Dong Hu ◽

YiXuan Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Signaling Pathways ◽

Erk Signaling ◽

Migration And Invasion ◽

C Reactive Protein ◽

Reactive Protein ◽

Co Precipitation ◽

Hcc Cells

Abstract Background C-reactive protein (CRP), an acute phase protein, has been increasingly implicated in various tumors, and the role of CRP is positively correlated with invasion and metastasis in hepatocellular carcinoma cells. However, the mechanism of CRP affecting HCC progression remains poorly investigated. The present study investigated the role of CRP in HCC and the underlying mechanisms. Methods In the current study, CRP overexpression and suppression expression experiments were used to evaluate the effect of CRP on malignant biological behavior of liver cancer cells in vitro. Then iTRAQ-mass spectrometry analysis was used to identify CRP co-immunoprecipitation complexes. Detecting the interaction between CRP and Eph receptor B3 (EphB3) by co-precipitation. Moreover, immunofluorescence colocalization and co-precipitation, and Western Blot, in vivo model were applied to study the molecular mechanism of CRP affecting the development of Hepatocellular Carcinoma. Results We first found that CRP was significantly upregulated in HCC tissues and HCC cells, the expression level correlated with the metastatic ability of HCC cells. Knockdown of CRP significantly suppresses migration and invasion capacity in HCC cells. Through a proteomic analysis of CRP co-immunoprecipitation complexes, the EphB3 was identified as a new CRP interactor. Then we found that the expression and functions of EphB3 were consistent with CRP in HCC. In addition, co-immunoprecipitation and immunofluorescence assays suggested that EphB3 was able to interact with MAPK/ERK to activate MAPK/ERK signaling pathways. Furthermore, we showed that CRP can induce the phosphorylation of MAPK/ERK by binding EphB3. CRP also significantly stimulated MMP-9 expression, mainly by activating HIF-1α via the MAPK/ERK pathways. Conclusions Our findings showed that CRP increased HCC cells migration and invasion by binding EphB3 to activate MAPK/ERK signaling pathways. It suggested that CRP may become a prognostic factor and a potential therapeutic target for liver cancer.

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MicroRNA-139-3p Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by Repressing ANXA2R

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15178798885361 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1391-1399 ◽

Cited By ~ 5

Author(s):

Zeng Cheng Zou ◽

Min Dai ◽

Zeng Yin Huang ◽

Yi Lu ◽

He Ping Xie ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Cell Growth ◽

Mouse Model ◽

Migration And Invasion ◽

Tumor Growth And Metastasis ◽

Underlying Mechanisms ◽

Hcc Cells

The direct roles of miR-139-3p on hepatocellular carcinoma (HCC) cell growth and metastasis remain poorly understood. We attempted to demonstrate the regulatory role of miR-139-3p in HCC progression and its underlying mechanisms. Here we showed that miR-139-3p expression was significantly reduced in the HCC tissues compared to paratumor tissues. Exogenous overexpression of miR-139-3p inhibited the migration and invasion of HCC cells, whereas downregulation of miR-139-3p was able to induce HCC HepG2 and SNU-449 cell migration and invasion. In addition, miR-139-3p inhibited HCC growth and lung metastasis in an in vivo mouse model, which is mainly regulated by annexin A2 receptor (ANXA2R). Finally, we identified that the expression of miR-139-3p was inversely correlated with ANXA2R expression in human HCC tissue. All these results demonstrated that miR-139-3p inhibited the metastasis process in HCC by downregulating ANXA2R expression.

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Sufentanil Inhibits Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells by Upregulating miRNA-204

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2561 ◽

2021 ◽

Vol 11 (4) ◽

pp. 718-724

Author(s):

Jiuwu Zhuo ◽

Yishan Zheng ◽

Wanying Hu ◽

Guoping Yin

Keyword(s):

Hepatocellular Carcinoma ◽

Biological Function ◽

Transfection Efficiency ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Qrt Pcr ◽

Pi3k Signaling Pathway ◽

Hep3b Cells ◽

Underlying Mechanisms ◽

Hcc Cells

Sufentanil is a powerful analgesic that acts on μ-receptors, but there are few studies on sufentanil in cancer. The biological function and underlying mechanisms of sufentanil on the hepatocellular carcinoma (HCC) cells were explored in the present study. HCC cells were first treated with different concentrations of sufentanil and the most optimum concentration of sufentanil was determined. The expression of miR-204 in HCC cells was changed by transfected with miR-204 inhibitor and the transfection efficiency was assessed by qRT-PCR. CCK-8, wound-healing and Transwell assays were performed to evaluate the proliferation, migration and invasion of HCC cells, respectively. The level of AKT and PI3K phosphorylation (p-AKT and p-PI3K) were assessed by western blot analysis. Our results demonstrated that sufentanil effectively inhibited cell proliferation,migration and invasion in both Huh7 and Hep3B cells, and significantly decreased the expression of p-AKT and p-PI3K. In addition, miR-204 was upregulated in Huh7 and Hep3B cells treated with sufentanil, and low expression of miR-204 attenuated the damage of sufentanil on the viability of Huh7 and Hep3B cells. Taken together, sufentanil suppressed the proliferation, migration and invasion of HCC cells via inhibiting AKT/PI3K signaling pathway by targeting miR-204.

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LncRNA SAMMSON negatively regulates miR-9-3p in hepatocellular carcinoma cells and has prognostic values

Bioscience Reports ◽

10.1042/bsr20190615 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 3

Author(s):

Shouzhang Yang ◽

Huajie Cai ◽

Bingren Hu ◽

Jinfu Tu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Cancer Cell ◽

Carcinoma Cells ◽

Migration And Invasion ◽

Cancer Cell Migration ◽

Expression Levels ◽

Cell Migration And Invasion ◽

Hcc Cells

Abstract In the present study, we investigated the role of lncRNA SAMMSON in hepatocellular carcinoma (HCC). We found that SAMMSON was up-regulated in HCC tissues, and patients with high levels of SAMMSON in HCC tissues had significantly lower overall rate within 5 years after admission. miR-9-3p was down-regulated in HCC tissues and inversely correlated with SAMMSON. SAMMSON expression was not significantly affected by HBV and HCV infections in HCC patients. In HCC cells, SAMMSON overexpression resulted in down-regulated miR-9-3p expression, while miR-9-3p overexpression caused no significant changes in expression levels of SAMMSON. SAMMSON overexpression led to increased, while miR-9-3p overexpression resulted in decreased migration and invasion rates of HCC cells. Therefore, SAMMSON negatively regulated miR-9-3p in HCC cells to promote cancer cell migration and invasion.

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