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

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.

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

2021 ◽  
Author(s):  
Yi Xuan Yang ◽  
Sha She ◽  
Min Yang ◽  
Shi Ying Li ◽  
Huai Dong Hu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Carcinoma Cells ◽  
Erk Signaling ◽  
Migration And Invasion ◽  
C Reactive Protein ◽  
Eph Receptor ◽  
Reactive Protein ◽  
Underlying Mechanisms ◽  
Hcc Cells

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.

scholarly journals Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Casein Kinase 1 ◽  
Mouse Xenograft Model ◽  
Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

scholarly journals Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qingmin Chen ◽  
Ludong Tan ◽  
Zhe Jin ◽  
Yahui Liu ◽  
Ze Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Hcc Cells

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

scholarly journals Telocytes Promote the Metastasis of Hepatocellular Carcinoma by Activating ERK Signaling Pathway and Sponging miR-942-3p to Impact MMP9

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Cancer Tissue ◽  
Proliferative Potential ◽  
Cancer Tissues ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.

scholarly journals MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Xiaohui Duan ◽  
Wei Li ◽  
Peng Hu ◽  
Bo Jiang ◽  
Jianhui Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Growth ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan–Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC.

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

2018 ◽  
Vol 26 (9) ◽  
pp. 1391-1399 ◽  
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.

Telocytes Promote Hepatocellular Carcinoma by Activating The ERK Signaling Pathway and miR-942-3p/MMP9 Axis

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
Peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Metastatic Cancer ◽  
Erk Signaling ◽  
Mmp9 Expression ◽  
Cancer Tissues

Abstract Background In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but theirs functions in HCC are still unknown. Methods TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using 3 types of liver cancer cell lines in vivo. Results TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; however, this had no significant effect on TC proliferation and apoptosis. miR-942-3p suppressed MMP9 expression in TCs. Conclusion Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.

STAT3 and AKT signaling pathways mediate oncogenic role of NRSF in hepatocellular carcinoma

2020 ◽  
Vol 52 (10) ◽  
pp. 1063-1070
Author(s):  
Ming Ma ◽  
Yunhe Zhou ◽  
Ruilin Sun ◽  
Jiahao Shi ◽  
Yutong Tan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Zinc Finger Protein ◽  
Akt Signaling ◽  
Nervous System Development ◽  
Migration And Invasion ◽  
Tumor Type ◽  
Dependent Manner ◽  
Rnai Technology

Abstract Neuron-restrictive silencer factor (NRSF) is a zinc finger protein that acts as a negative transcriptional regulator by recruiting histone deacetylases and other co-factors. It plays a crucial role in nervous system development and is recently reported to be involved in tumorigenesis in a tumor type-dependent manner; however, the role of NRSF in hepatocellular carcinoma (HCC) tumorigenesis remains unclear. Here, we found that NRSF expression was up-regulated in 27 of 49 human HCC tissue samples examined. Additionally, mice with conditional NRSF-knockout in the liver exhibited a higher tolerance against diethylnitrosamine (DEN)-induced acute liver injury and were less sensitive to DEN-induced HCC initiation. Our results showed that silencing NRSF in HepG2 cells using RNAi technology significantly inhibited HepG2 cell proliferation and severely hindered their migration and invasion potentials. Our results demonstrated that NRSF plays a pivotal role in promoting DEN-induced HCC initiation via a mechanism related to the STAT3 and AKT signaling pathways. Thus, NRSF could be a potential therapeutic target for treating human HCC.

scholarly journals microRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract BackgroundIncreasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. MethodsWe carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.ResultsThis study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusionour study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

scholarly journals MicroRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract Background: Increasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. Methods: We carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.Results: This study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusion: our study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

Sign in / Sign up

Export Citation Format

Share Document