scholarly journals Swertiamarin suppresses proliferation, migration, and invasion of hepatocellular carcinoma cells via negative regulation of FRAT1

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Shufeng Xiao ◽  
Haoren Tang ◽  
Yao Bai ◽  
Renchao Zou ◽  
Zongfang Ren ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real Time ◽  
Cell Lines ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Signalling Pathway ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Hcc Cells

Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM’s impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/β-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/β-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.

CircRNA profiling identifies circRNF180 as a tumor suppressor in hepatocellular carcinoma

Epigenomics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 513-530
Author(s):  
Xi Zeng ◽  
Chao Tan ◽  
Meile Mo ◽  
Xiaoling Qin ◽  
Xiaoyun Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Real Time ◽  
Real Time Pcr ◽  
Expression Profiles ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Quantitative Real Time Pcr ◽  
Potential Biomarker ◽  
Hcc Cells

Aim: To explore the expression profiles and functions of circRNAs in hepatocellular carcinoma (HCC). Materials & methods: We obtained circRNA expression profiles through RNA sequencing. Expression levels of circRNAs were confirmed by quantitative real-time PCR. The effects on HCC progression were determined using Cell Counting Kit 8, clone formation and transwell assays. Results: We identified 114 upregulated and 144 downregulated circRNAs in HCC tissues. The results of quantitative real-time PCR showed that circGNAO1, circRNF180 and circMERTK were significantly downregulated in HCC tissues, whereas circSNX6 was significantly upregulated. CircRNF180 was associated with microvascular invasion. Overexpression of circRNF180 inhibits the proliferation, colony formation, migration and invasion of HCC cells. Conclusion: CircRNF180 may function as a tumor suppressor and could serve as a potential biomarker and therapeutic target in HCC.

scholarly journals Identification and Validation of the N6-Methyladenosine RNA Methylation Regulator YTHDF1 as a Novel Prognostic Marker and Potential Target for Hepatocellular Carcinoma

2020 ◽  
Vol 7 ◽  
Author(s):  
Saiyan Bian ◽  
Wenkai Ni ◽  
Mengqi Zhu ◽  
Qianqian Song ◽  
Jianping Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Biological Activities ◽  
Enrichment Analysis ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Rna Methylation ◽  
Hcc Cells

Purpose: N6-methyladenosine (m6A) RNA methylation has been implicated in various malignancies. This study aimed to identify the m6A methylation regulator-based prognostic signature for hepatocellular carcinoma (HCC) as well as provide candidate targets for HCC treatment.Methods: The least absolute shrinkage and selection operator (LASSO) analyses were performed to identify a risk signature in The Cancer Genome Atlas (TCGA) datasets. The risk signature was further validated in International Cancer Genome Consortium (ICGC) and Pan-Cancer Analysis of Whole Genomes (PCAWG) datasets. Following transfection of short hairpin RNA (shRNA) targeting YTHDF1, the biological activities of HCC cells were evaluated by Cell Counting Kit-8 (CCK-8), wound-healing, Transwell, flow cytometry, and xenograft tumor assays, respectively. The potential mechanisms mediated by YTHDF1 were predicted by overrepresentation enrichment analysis (ORA)/gene set enrichment analysis (GSEA) and validated by Western blotting.Results: Overexpression of m6A RNA methylation regulators was correlated with malignant clinicopathological characteristics of HCC patients. The Cox regression and LASSO analyses identified a risk signature with five m6A methylation regulators (KIAA1429, ZC3H13, YTHDF1, YTHDF2, and METTL3). In accordance with HCC cases in TCGA, the prognostic value of risk signature was also determined in ICGC and PCAWG datasets. Following analyzing the expression and clinical implications in TCGA and Gene Expression Omnibus (GEO), YTHDF1 was chosen for further experimental validation. Knockdown of YTHDF1 significantly inhibited the proliferation, migration, and invasion of HCC cells, as well as enhanced the apoptosis in vitro. Moreover, silencing YTHDF1 repressed the growth of xenograft tumors in vivo. Mechanism investigation indicated that YTHDF1 might promote the aggressive phenotypes by facilitating epithelial–mesenchymal transition (EMT) and activating AKT/glycogen synthase kinase (GSK)-3β/β-catenin signaling.Conclusion: The current study identified a robust risk signature consisting of m6A RNA methylation regulators for HCC prognosis. In addition, YTHDF1 was a potential molecular target for HCC treatment.

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 ORC6, Negatively Regulated by miR-1-3p, Promotes Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Hu Chen ◽  
Lequn Bao ◽  
Jianhua Hu ◽  
Dongde Wu ◽  
Xianli Tong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Hcc Cells

BackgroundIn recent years, microRNA-1-3p (miR-1-3p) has been linked to the progression of multiple cancers, whereas little is known about its role in hepatocellular carcinoma (HCC). Herein, we investigated the function of miR-1-3p in HCC, and its regulatory function on origin recognition complex subunit 6 (ORC6).MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expression levels of miR-1-3p and ORC6 mRNA in HCC samples and cell lines. ORC6 expression at the protein level was quantified by Western blot. After gain-of-function and loss-of-function models were established, cell counting kit-8 (CCK-8) assays, Transwell assays, flow cytometry, and 5-Ethynyl-2′-deoxyuridine (EdU) assay were performed for examining cell proliferation, migration, invasion, cell cycle, and apoptosis. The targeting relationship between miR-1-3p and ORC6 was confirmed with bioinformatic analysis and dual-luciferase reporter assays.ResultsThe expression of miR-1-3p was reduced in HCC samples and cell lines. Overexpression of miR-1-3p suppressed the proliferation, migration, and invasion, and induced cell-cycle arrest and apoptosis of HCC cells, whereas the opposite effects were induced by miR-1-3p inhibition. ORC6 is identified as a novel target of miR-1-3p, the expression of which is negatively correlated with miR-1-3p expression in HCC tissues. ORC6 overexpression facilitated the proliferation, migration, invasion, and cell cycle progression, and reduced apoptosis of HCC cells, whereas the opposite effects were induced by ORC6 knockdown. What is more, ORC6 overexpression counteracted the biological functions of miR-1-3p in HCC cells.ConclusionMiR-1-3p targets ORC6 to suppress the proliferation, migration, invasion, and cell cycle progression, and promote apoptosis of HCC cells.

scholarly journals CircRNA hsa_circ_0110102 Function as Anti-Oncogenic Gene in Hepatocellular Carcinoma Through Modulating miR-580-5p/CCL2 Pathway

2020 ◽  
Author(s):  
Xinxing Wang ◽  
Wei Sheng ◽  
Tao Xu ◽  
Jiawen Xu ◽  
Zhenhai Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Expression Levels ◽  
Cox 2 ◽  
Hcc Cells

Abstract Background: Circular RNAs (circRNAs) have been shown to have critical regulatory roles in tumor biology, whereas their contributions in hepatocellular carcinoma (HCC) still remains enigmatic. The purpose of this study was to investigate the molecular mechanisms involved in hsa_circ_0110102 in the occurrence and development of HCC. Methods: The expression levels of hsa_circ_0110102 in HCC cell lines and tissues were estimated by RT-qPCR assay. The proliferation, migration, and invasion of HCC cells were determined by CCK-8 and transwell assay. The western blot and ELISA were employed to examine the related-protein and cytokine expression. The association between miR-580-5p and hsa_circ_0110102 or CCL2 was predicted and affirmed by dual-luciferase reporter assay and RNA pull-down.Results: hsa_circ_0110102 was significantly down-regulated in HCC cell lines and tissues, low hsa_circ_0110102 expression levels were associated with poor prognosis. Knockdown hsa_circ_0110102 significantly inhibited cell proliferation, migration and invasion. In addition, luciferase assay and RNA pull-down assay indicating that hsa_circ_0110102 function as sponge for miR-580-5p. Moreover, miR-580-5p which could directly bind to the 3’-UTR of CCL2 and induce its expression, then active the COX-2/PGE2 pathway in macrophage via FoxO1 in p38 MAPK dependent manner. Furthermore, the Δ256 mutant of FoxO1 showed no activation effect. Conclusion: hsa_circ_0110102 act as a sponge for miR-580-5p and decreased CCL2 secretion in HCC cells, then inhibits pro-inflammatory cytokine release from activated macrophage by regulating the COX-2/PGE2 pathway. These results indicating that hsa_circ_0110102 serves as a potential prognostic predictor or therapeutic target for HCC.

scholarly journals Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Li-Man Li ◽  
Chang Chen ◽  
Ruo-Xi Ran ◽  
Jing-Tao Huang ◽  
Hui-Lung Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Tumor Development ◽  
Plasminogen Activator Inhibitor ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Blood Samples

The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has been shown to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit‐8 (CCK‐8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR‐145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.

scholarly journals Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Chenggang Zhao ◽  
Lizhu Hu ◽  
Delong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Xenograft Model ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Self Renewal

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

scholarly journals The Inhibitory Effect of KIAA1456 on the Proliferation and Metastasis of Epithelial Ovarian Cancer Through SSX1 and AKT Signaling Pathway

2021 ◽  
Author(s):  
Yingfeng Zhang ◽  
Yanhong Gao ◽  
Congcong Sun ◽  
Yanhua Mao ◽  
Benyuan Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Signalling Pathway ◽  
Migration And Invasion ◽  
Ovarian Tumours ◽  
Proliferation And Metastasis ◽  
Epithelial Ovarian Tumours

Abstract Background: KIAA1456 is effective in the inhibition of tumorigenesis. We previously confirmed that KIAA1456 inhibits cell proliferation and metastasis in epithelial ovarian tumours. In the current study, the specific molecular mechanisms and clinical significance of KIAA1456 underlying the repression of epithelial ovarian cancer were investigated.Methods: Immunohistochemistry was used to evaluate the protein expression of KIAA1456 and SSX1 in epithelial ovarian tumours and normal ovarian tissues. The relationship of KIAA1456 and SSX1 with overall survival of patients with epithelial ovarian cancer was analysed with Kaplan–Meier survival curve and log-rank tests. KIAA1456 was overexpressed and silenced in HO8910PM cells with a lentivirus. The anticancer activity of KIAA1456 was tested by CCK8, plate clone formation assay, flow cytometry, wound healing assay and Transwell invasion assay. Xenograft tumour models were used to investigate the effects of KIAA1456 on tumour growth in vivo. Bioinformatics analyses of microarray profiling indicated that SSX1 and the PI3K/AKT signalling pathway were differentially expressed in KIAA1456-overexpressing and control cells. Therefore, the biological function of HO8910PM cotransfected with KIAA1456- and SSX1-overexpressing cells was detected to validate the rescue effect of SSX1. The downstream factors of PI3K/AKT that are related to cell growth and apoptosis, including p-AKT, PCNA, MMP9, CyclinD1 and Bcl-2, were detected by Western blot analysis.Results: KIAA1456 expression was lower in epithelial ovarian tumours than in normal ovarian tissues. Its expression level negatively correlated with pathological grade. Pearson’s correlation analysis showed that KIAA1456 negatively correlated with SSX1 expression. The overexpression of KIAA1456 in HO8910PM cells inhibited proliferation, migration and invasion and promoted apoptosis. By contrast, the silencing of KIAA1456 resulted in the opposite behaviour. A xenograft tumour experiment showed that KIAA1456 overexpression inhibited tumour growth in vivo. Mechanistically, the overexpression of KIAA1456 inhibited SSX1 expression and AKT phosphorylation in HO8910PM cells, causing the inactivation of the AKT signalling pathway and eventually reducing the expression of PCNA, CyclinD1, MMP9 and Bcl2. Similarly, the silencing of KIAA1456 resulted in the opposite behaviour. Finally, SSX1 overexpression could partially reverse the KIAA1456-induced biological effect.Conclusion: KIAA1456 may serve as a tumour suppressor via the inactivation of SSX1 and the AKT pathway, providing a promising therapeutic target for epithelial ovarian cancers.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

scholarly journals Angiotensin II Enhances Proliferation and Inflammation through AT1/PKC/NF-κB Signaling Pathway in Hepatocellular Carcinoma Cells

2016 ◽  
Vol 39 (1) ◽  
pp. 13-32 ◽  
Author(s):  
Yuanyuan Ji ◽  
Zhidong Wang ◽  
Zongfang Li ◽  
Aijun Zhang ◽  
Yaofeng Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Angiotensin Ii ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Hepatocyte Proliferation ◽  
Nuclear Antigen ◽  
Ang Ii ◽  
Hcc Cells

Background/Aims: The pathogenesis of hepatocellular carcinoma (HCC) is mainly characterized by persistent cycles of liver injury, inflammation, and compensatory hepatocyte proliferation. Angiotensin II (Ang II) behaves as an endogenous pro-inflammatory molecule playing a significant role in HCC, however, the molecular link between Ang II, proliferation and inflammation remains unclear. Methods: Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with Ang II at the indicated concentrations for 24, 48, 72 h. MTT, BrdU ELISA, plate colony formation assay, immunohistochemistry, ELISA, small-interfering RNA(siRNA) transfection, quantitative real-time PCR and western blot were applied to assess their functional, morphological and molecular mechanisms in HCC cell lines. Results: High expression of Ang II type 1 receptor (AT1) and low expression of AT2 in HCC cells and tissues were found. Next, Ang II could significantly enhance cell growth and proliferation. Albeit Ang II slightly increased the percentage of HCC cells in the G0/G1 phase using flow cytometry analysis, no statistically significant alterations were shown. Further studies suggested that Ang II could directly induce proliferation associated proteins C-myc and proliferating cell nuclear antigen (PCNA) expressions, and inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) productions in HCC cells. Interestingly, blocking AT1 and AT1 siRNA evidently inhibited Ang II-induced cell proliferation and inflammatory responses in HCC cells. More importantly, these effects may be mediated by AT1/PKC/NF-κB signaling pathway in HCC cell lines. Conclusions: The results propose that Ang II/AT1/PKC/NF-κB signaling pathway is necessary for proliferation and inflammation of HCC cells, which increases our understanding of the pathogenesis and provides clues for developing new strategies against Ang II-related progress of HCC.

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