scholarly journals Downregulation of Heparanase Expression Results in Suppression of Invasion, Migration, and Adhesion Abilities of Hepatocellular Carcinoma Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Peng Chen ◽  
Jun-Sheng Luo ◽  
Ye Tian ◽  
Chen-Lin Nie ◽  
Wei Cui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Invasion ◽  
Malignant Tumors ◽  
Carcinoma Cells ◽  
Adherence Rate ◽  
Rt Pcr ◽  
Invasion And Migration ◽  
Normal Hepatocyte ◽  
And Migration ◽  
Hcc Cells

Objective.Heparanase (HPSE) is high-expressed in most malignant tumors including hepatocellular carcinoma (HCC) and promotes cancer cell invasion and migration. The aim of the study is to explore whether HPSE enhances adhesion in metastasis of HCC cells.Methods. HPSE expressions in human HCC cells were measured with real-time RT-PCR and Western blot analysis. Four recombinant miRNA vectors pcDNATM6.2-GW/EmGFP-miR-HPSE (pmiR-HPSE) were transfected into HCCLM3 cell. HPSE expression in transfected cell was measured. The cell invasion, migration, and adhesion abilities were detected, respectively.Results. Both HPSE mRNA and protein relative expression levels were higher in HepG2, BEL-7402, and HCCLM3 cells than those in normal hepatocyte (P<0.05). HPSE showed highest expression level in HCCLM3 cell (P<0.05). Transfection efficiencies of four miRNA vectors were 75%–85%. The recombinant vectors significantly decreased HPSE expression in transfected HCCLM3 cells (P<0.01), and pmiR-HPSE-1 showed best interference effect (P<0.05). pmiR-HPSE-1 significantly decreased the penetrated and migrating cells numbers and adherence rate of HCCLM3 cells (P<0.05).Conclusion. HPSE is a potentiator of cell adhesion in metastasis of HCC.

scholarly journals Hsa_circ_0013290 Acts as Cancer-Promoting Gene in Hepatocellular Carcinoma

2021 ◽  
Vol 28 ◽  
pp. 107327482110556
Author(s):  
Xi Luo ◽  
Yicun Liu ◽  
Han Li ◽  
Tiaochun Cheng ◽  
Jianjun Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Subcellular Location ◽  
Cell Counting ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration ◽  
Hcc Cells

Background As a new class of non-coding RNAs, circRNAs have been recently reported to be involved in the tumorigenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a novel circRNA (hsa_circ_0013290) in hepatocellular carcinoma (HCC). Methods Relative hsa_circ_0013290 expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The subcellular location of hsa_circ_0013290 was performed by RNA subcellular isolation and fluorescence in situ hybridization (FISH) assays. The effect of hsa_circ_0013290 on proliferation was detected by Cell Counting Kit-8 (CCK-8) assays. The effect of hsa_circ_0013290 on cell cycle distribution and apoptosis was detected by flow cytometry. The invasion and migration abilities of hsa_circ_0013290 were detected by transwell assays. Results Hsa_circ_0013290 is significantly upregulated in HCC cell lines and mainly located in cytoplasm of HCC cells. Hsa_circ_0013290 overexpression promotes cell invasion and migration and inhibits cell apoptosis. In contrast, hsa_circ_0013290 knockdown impedes cell invasion and migration and accelerates cell apoptosis. However, hsa_circ_0013290 did not affect cell proliferation. Conclusions Hsa_circ_0013290 is overexpressed in HCC cell lines and is mainly located in the cytoplasm of HCC cells. Hsa_circ_0013290 promotes cell invasion and migration, and inhibits cell apoptosis.

scholarly journals TO901317 inhibits the development of hepatocellular carcinoma by LXRα/Glut1 decreasing glycometabolism

2019 ◽  
Vol 316 (5) ◽  
pp. G598-G607 ◽  
Author(s):  
Ting Xiong ◽  
Zihan Li ◽  
Xuelong Huang ◽  
Kaiqiang Lu ◽  
Weiquan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Cell Invasion ◽  
Glucose Concentration ◽  
Glucose Transporter ◽  
Liver X Receptor ◽  
Invasion And Migration ◽  
And Migration ◽  
Hcc Cells

This study was conducted to observe the effect and possible mechanism of TO901317 in vivo and in vitro to provide a new basis for the targeted therapy of hepatocellular carcinoma (HCC). The expressions of liver X receptor (LXR)-α, glucose transporter (Glut)-1, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase (MMP)-9 were analyzed from HCC public database (NCBI PubMed database). The result showed that LXRα was downregulated, whereas Glut1, PCNA, and MMP9 were upregulated in human HCC compared with normal liver. Furthermore, LXRα mRNA was negatively correlated with Glut1 mRNA. At the same time, HCC cells were cultivated in vitro and axillary injected in nude mice to establish the xenograft model. The xenograft in the TO901317-treated group was slower and smaller than the control group. The protein expression of LXRα, Glut1, and MMP9 could be detected by Western blot and glucose level. As a result, TO901317 could inhibit the cell proliferation of HCC in a dose-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. With the increase of TO901317 concentration, the cellular glucose concentration and ATP level were gradually decreased. Western blot results showed TO901317 could upregulate LXRα expression but downregulate MMP9 and Glut1 expression. Transwell and wound-healing analysis confirmed that, by increasing the concentration of TO901317, the cell invasion and migration were both decreased. LXRα small-interfering RNA (siRNA) could relieve the suppression effect of TO901317 on the cell invasion and migration and the expression of LXRα, Glut1, and MMP9. The glucose concentration was also raised. TO901317 could repress the progress of HCC cells by reducing the glucose concentration, upregulating LXRα expression, but downregulating the expression of Glut1 and MMP9. NEW & NOTEWORTHY This subject confirmed that TO901317, a specific liver X receptor agonist, could inhibit the progression of liver cancer through upregulating liver X receptor-α, downregulating the expression of glucose transporter-1 and matrix metalloproteinase-9, and decreasing the glucose content in SMMC-7721 and HepG2 cells.

Delivery of microRNA-21-sponge and pre-microRNA-122 by MS2 virus-like particles to therapeutically target hepatocellular carcinoma cells

2021 ◽  
pp. 153537022110356
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Rongxue Peng ◽  
Jinming Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Hepatocellular Carcinoma Cells ◽  
Virus Like Particles ◽  
Invasion And Migration ◽  
Mrna Targets ◽  
And Migration ◽  
Microrna Dysregulation ◽  
Hcc Cells

MicroRNAs are related to the development of hepatocellular carcinoma and can serve as potential therapeutic targets. Therapeutic strategies increasing tumor-suppressive microRNAs and reducing oncogenic microRNAs have been developed. Herein, the effects of simultaneously altering two microRNAs using MS2 virus-like particles were studied. The sequences of microRNA-21-sponge and pre-microRNA-122 were connected and cloned into a virus-like particle expression vector. Virus-like particles containing microRNA-21-sponge and pre-microRNA-122 sequences were prepared and crosslinked with a cell-specific peptide targeting hepatocellular carcinoma cells. Delivery effects were studied using RT-qPCR and functional assays to investigate the level of target mRNAs, cell toxicity, and the effects of proliferation, invasion, and migration. Virus-like particles delivered miR-21-sponge into cells, with the Ct value reaching 10 at most. The linked pre-miR-122 was processed into mature miR-122. The mRNA targets of miR-21 were derepressed as predicted and upregulated 1.2–2.8-fold, and the expression of proteins was elevated correspondingly. Proliferation, migration, and invasion of HCC cells were inhibited by miR-21-sponge. Simultaneous delivery of miR-21-sponge and miR-122 further decreased proliferation, migration, and invasion by up to 34%, 63%, and 65%, respectively. And the combination promoted the apoptosis of HCC cells. In conclusion, delivering miR-21-sponge and miR-122 using virus-like particles modified by cell-specific peptides is an effective and convenient strategy to correct microRNA dysregulation in hepatocellular carcinoma cells and is a promising therapeutic strategy for hepatocellular carcinoma.

scholarly journals Anti-neoplastic Effect of Ginkgolide C through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8303
Author(s):  
Min Hee Yang ◽  
Seung Ho Baek ◽  
Jae-Young Um ◽  
Kwang Seok Ahn
Keyword(s):  
Hepatocellular Carcinoma ◽  
Invasion And Migration ◽  
Oncogenic Pathways ◽  
Tumor Growth And Metastasis ◽  
And Migration ◽  
Induced Apoptosis ◽  
Interfering Rna ◽  
Hepatocyte Growth ◽  
Hcc Cells ◽  
Met Phosphorylation

Ginkgolide C (GGC) derived from Ginkgo biloba, has been reported to exhibit various biological functions. However, the anti-neoplastic effect of GGC and its mechanisms in liver cancer have not been studied previously. Hepatocyte growth factor (HGF)/c-mesenchymal–epithelial transition receptor (c-Met) pathway can regulate tumor growth and metastasis in hepatocellular carcinoma (HCC) cells. This study aimed to evaluate the anti-neoplastic effect of GGC against HCC cells and we observed that GGC inhibited HGF-induced c-Met and c-Met downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. In addition, GGC also suppressed the proliferation of expression of diverse tumorigenic proteins (Bcl-2, Bcl-xL, Survivin, IAP-1, IAP-2, Cyclin D1, and COX-2) and induced apoptosis. Interestingly, the silencing of c-Met by small interfering RNA (siRNA) mitigated c-Met expression and enhanced GGC-induced apoptosis. Moreover, it was noted that GGC also significantly reduced the invasion and migration of HCC cells. Overall, the data clearly demonstrate that GGC exerts its anti-neoplastic activity through modulating c-Met phosphorylation and may be used as an effective therapy against HCC.

Chondroitin polymerizing factor (CHPF) contributes to malignant proliferation and migration of hepatocellular carcinoma cells

2020 ◽  
Vol 98 (3) ◽  
pp. 362-369
Author(s):  
Qigang Xu ◽  
Wei Lin ◽  
Chonglin Tao ◽  
Xiaming Huang ◽  
Junjian Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
Malignant Tumors ◽  
Mrna And Protein Expression ◽  
Advanced Stages ◽  
Human Digestive System ◽  
And Migration ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the human digestive system, and has been recognized as a serious threat to public health worldwide. This study explored the role of chondroitin polymerizing factor (CHPF) in the development and metastasis of HCC. Immunohistochemistry analysis was performed to detect CHPF expression in HCC tissues and para-carcinoma tissues. qRT-PCR and Western blot analysis were used to determine the mRNA and protein expression of CHPF. MTT assays, colony formation assays, and flow cytometry were used to evaluate the cell proliferation, colony formation, and cell apoptosis, respectively. Wound-healing and Transwell assays were performed to evaluate cell migration. The results show that CHPF was not only up-regulated in HCC tissues compared with para-carcinoma tissues, but was also related with more advanced stages of HCC. Further studies revealed that CHPF knockdown significantly inhibited cell proliferation and colony formation, and induce cell apoptosis of HCC cells. Moreover, suppressing the expression of CHPF reduced the migration and invasiveness of HCC cells. In conclusion, we demonstrated that CHPF plays important roles in the development and progression of HCC, and high expression levels of HCC may be related with poorer prognosis. The results from this study may provide a potential therapeutic target for HCC treatment.

scholarly journals Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 490 ◽  
Author(s):  
Qiu-Ping Liu ◽  
Qing Luo ◽  
Bin Deng ◽  
Yang Ju ◽  
Guan-Bin Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Migration ◽  
Aerobic Glycolysis ◽  
Mapk Signaling ◽  
Carcinoma Cells ◽  
Metabolic Reprogramming ◽  
Signaling Cascade ◽  
And Migration ◽  
Hcc Cells

Increased extracellular matrix (ECM) stiffness and metabolic reprogramming of cancer cells are two fundamental mediators of tumor progression, including hepatocellular carcinoma (HCC). Yet, the correlation between ECM stiffness and excessive aerobic glycolysis in promoting the development of HCC remains unknown. Here, we demonstrated that stiffer ECM promotes HCC cell migration depending on their accelerated aerobic glycolysis. Our results also indicated that stiffer ECM-induced YAP activation plays a major role in promoting aerobic glycolysis of HCC cells. Moreover, we showed that JNK and p38 MAPK signaling are critical for mediating YAP activation in HCC cells. Together, our findings established that the MAPK-YAP signaling cascade that act as a mechanotransduction pathway is essential for promoting HCC cell aerobic glycolysis and migration in response to ECM stiffness.

MicroRNA-194 inhibits cell invasion and migration in hepatocellular carcinoma through PRC1-mediated inhibition of Wnt/β-catenin signaling pathway

2019 ◽  
Vol 51 (9) ◽  
pp. 1314-1322 ◽  
Author(s):  
Hui Tang ◽  
Hui Zhao ◽  
Zhen-Yu Yu ◽  
Xiao Feng ◽  
Bin-Sheng Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
And Migration

scholarly journals Alpha-Fetoprotein Regulates the Expression of Immune-Related Proteins through the NF-κB (P65) Pathway in Hepatocellular Carcinoma Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Qiu-ting Li ◽  
Meng-jun Qiu ◽  
Sheng-li Yang ◽  
Xiefan Fang ◽  
Xiao-xiao He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Protein A ◽  
Radical Resection ◽  
Alpha Fetoprotein ◽  
Control Group ◽  
Invasion And Migration ◽  
Immune Genes ◽  
And Migration ◽  
Hcc Cells

Background. The prognosis of patients with hepatocellular carcinoma (HCC) is poor, with 60% to 70% of patients developing recurrence and metastasis within five years of radical resection. Alpha-fetoprotein (AFP) plays a significant role in predicting the recurrence and metastasis of HCC after surgery. However, its role in modulating tumor immunity has not been investigated. Our objective was to examine the effect of AFP on the expression of B7 family and activation of the NF-κB (P65) pathway in HCC. Methods. We generated human hepatoma SMMC-7721 cell lines with or without recombinant AFP transfection (AFPup and control groups). Colony formation assay, Transwell invasion assay, and wound healing assay were used to detect the function of AFP. Liver cancer xenografts were made in BALB/c nude male mice (N = 6 per group). After 28 days of inoculation, the expression of immune genes in the HCC tissues, including PD-L (B7-H1), B7-H3, B7-H4, and P65, was evaluated by quantitative real-time PCR (qPCR) and western blot. In addition, immunofluorescence was used to determine the subcellular localization of the P65 protein, a key factor in the NF-κB pathway. An online HCC patients’ dataset was also used to detect the connection between AFP and P65. Results. Overexpression of AFP could enhance proliferation, invasion, and migration of HCC cells. Both qPCR and western blot results demonstrated that the expressions of PD-L1, B7-H4, and P65 were significantly higher in the AFP group compared to the controls (P<0.05). Immunofluorescence results indicated that the majority of the P65 protein was located in the cytoplasm in the control group but was translocated to the nucleus in the AFPup group. The Spearman correlation coefficient confirms that AFP has a positive correlation with P65 in HCC patients (R = 0.33, P=0.05). Conclusion. AFP could enhance proliferation, invasion, and migration in HCC cells. The upregulation of AFP would increase the PD-L1 and B7-H4 mRNA and protein expression in HCC tissues through the upregulation and activation of the P65 protein.

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