scholarly journals TRAIL promotes hepatocellular carcinoma apoptosis and inhibits proliferation and migration via interacting with IER3

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shihai Liu ◽  
Jing Qiu ◽  
Guifang He ◽  
Weitai He ◽  
Changchang Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Necrosis ◽  
Transformed Cells ◽  
Apoptotic Death ◽  
And Migration ◽  
Necrosis Factor ◽  
Hcc Cells ◽  
Proliferation And Migration

AbstractTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce substantial cytotoxicity in tumor cells but rarely exert cytotoxic activity on non-transformed cells. In the present study, we therefore evaluated interactions between TRAIL and IER3 via co-immunoprecipitation and immunofluorescence analyses, leading us to determine that these two proteins were able to drive the apoptotic death of hepatocellular carcinoma (HCC) cells and to disrupt their proliferative and migratory abilities both in vitro and in vivo. From a mechanistic perspective, we determined that TRAIL and IER3 were capable of inhibiting Wnt/β-catenin signaling. Together, these results indicate that TRAIL can control the pathogenesis of HCC at least in part via interacting with IER3 to inhibit Wnt/β-catenin signaling, thus indicating that this TRAIL/IER3/β-catenin axis may be a viable therapeutic target in HCC patients.

LncRNA HCG18 contributes to the progression of hepatocellular carcinoma via miR-214-3p/CENPM axis

2020 ◽  
Vol 168 (5) ◽  
pp. 535-546 ◽  
Author(s):  
Yuepei Zou ◽  
Zhonghua Sun ◽  
Shuangming Sun
Keyword(s):  
Hepatocellular Carcinoma ◽  
Messenger Rna ◽  
Animal Experiments ◽  
Non Coding Rna ◽  
Diphenyltetrazolium Bromide ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

Abstract Long non-coding RNA (lnc) HCG18 has been reported to contribute progression of a variety of tumours. However, its roles in hepatocellular carcinoma (HCC) remains unknown. In the current study, we intended to uncover the biological functions of HCG18 in HCC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression of HCG18, microRNA-214-3p (miR-214-3p) and centromere protein M (CENPM) messenger RNA (mRNA). The role of HCG18 in the growth and migration were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, wound healing assay and flow cytometry in vitro and animal experiments in vivo. The results showed that HCG18 was highly expressed in HCC tissues. HCG18 silencing inhibited the proliferation and migration while induced the apoptosis of HCC cells. Besides, miR-214-3p was down-regulated in HCC cells. Further experiments revealed that miR-214-3p could directly bind to HCG18 and exerted an anti-tumour role to counteracted siHCG18-1-mediated influence in HCC cells. Moreover, miR-214-3p could directly interact with CENPM mRNA and down-regulating the expression of CENPM. While HCG18 could up-regulate the expression of CENPM through acting as a sponge of miR-214-3p. Therefore, those results suggested HCG18 functioned as an oncogene to promote the proliferation and migration of HCC cells via miR-214-3p/CENPM axis.

scholarly journals Linc-SCRG1 accelerates progression of hepatocellular carcinoma as a ceRNA of miR26a to derepress SKP2

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Jie Hu ◽  
Cui Zhou ◽  
Xin Luo ◽  
Sheng-Zheng Luo ◽  
Zheng-Hong Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Colony Formation ◽  
S Phase ◽  
Luciferase Reporter ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

Abstract Background Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear. Methods To explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models. Results LincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a. Conclusions LincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Heyun Zhang ◽  
Zhangyu Zheng ◽  
Rongqin Zhang ◽  
Yongcong Yan ◽  
Yaorong Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Histone Methylation ◽  
Cell Growth And Migration ◽  
Histone 3 ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Proliferation And Migration

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

scholarly journals Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nataša Pavlović ◽  
Carlemi Calitz ◽  
Kess Thanapirom ◽  
Guiseppe Mazza ◽  
Krista Rombouts ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Tumor Burden ◽  
And Migration ◽  
Hcc Cells ◽  
Proliferation And Migration

Hepatocellular carcinoma (HCC) is a liver tumor that usually arises in patients with cirrhosis. Hepatic stellate cells are key players in the progression of HCC, as they create a fibrotic micro-environment and produce growth factors and cytokines that enhance tumor cell proliferation and migration. We assessed the role of endoplasmic reticulum (ER) stress in the cross-talk between stellate cells and HCC cells. Mice with a fibrotic HCC were treated with the IRE1α-inhibitor 4μ8C, which reduced tumor burden and collagen deposition. By co-culturing HCC-cells with stellate cells, we found that HCC-cells activate IREα in stellate cells, thereby contributing to their activation. Inhibiting IRE1α blocked stellate cell activation, which then decreased proliferation and migration of tumor cells in different in vitro 2D and 3D co-cultures. In addition, we also observed cell-line-specific direct effects of inhibiting IRE1α in tumor cells.

scholarly journals Exosomal hsa_circ_0004658 derived from RBPJ overexpressed-macrophages inhibits hepatocellular carcinoma progression via miR-499b-5p/JAM3

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Lei Zhang ◽  
Jing Zhang ◽  
Pengfei Li ◽  
Ting Li ◽  
Zhiqin Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Mouse Xenograft Model ◽  
Rna Immunoprecipitation ◽  
And Migration ◽  
Hcc Cells

AbstractMacrophage-derived exosomes (Mφ-Exo) have multidimensional involvement in tumor initiation, progression, and metastasis, but their regulation in hepatocellular carcinoma (HCC) is not fully understood. RBPJ has been implicated in macrophage activation and plasticity. In this study we assess the role of exosomes derived from RBPJ-overexpressed macrophages (RBPJ+/+ Mφ-Exo) in HCC. The circular RNA (circRNA) profiles in RBPJ+/+ Mφ-Exo and THP-1-like macrophages (WT Mφ)-Exo was evaluated using circRNA microarray. CCK-8, Transwell, and flow cytometry analyses were used to evaluate the function of Mφ-Exo-circRNA on HCC cells. Luciferase reporter assays, RNA immunoprecipitation, and Pearson’s correlation analysis were used to confirm interactions. A nude mouse xenograft model was used to further analyze the functional significance of Mφ-Exo-cirRNA in vivo. Our results shown that hsa_circ_0004658 is upregulated in RBPJ+/+ Mφ-Exo compared to WT Mφ-Exo. RBPJ+/+ Mφ-Exo and hsa_circ_0004658 inhibits proliferation and promotes apoptosis in HCC cells, whereas hsa_circ_0004658 knockdown stimulated cell proliferation and migration but restrained apoptosis in vitro and promotes tumor growth in vivo. The effects of RBPJ+/+ Mφ-Exo on HCC cells can be reversed by the hsa_circ_0004658 knockdown. Mechanistic investigations revealed that hsa_circ_0004658 acts as a ceRNA of miR-499b-5p, resulting in the de-repression of JAM3. These results indicate that exosome circRNAs secreted from RBPJ+/+ Mφ inhibits tumor progression through the hsa_circ_0004658/miR-499b-5p/JAM3 pathway and hsa_circ_0004658 may be a diagnostic biomarker and potential target for HCC therapy.

scholarly journals FAM21C Promotes Hepatocellular Carcinoma Invasion and Metastasis by Driving Actin Cytoskeleton Remodeling via Inhibiting Capping Ability of CAPZA1

2022 ◽  
Vol 11 ◽  
Author(s):  
Yao Lu ◽  
Deng Huang ◽  
Baolin Wang ◽  
Bowen Zheng ◽  
Jialong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Actin Cytoskeleton ◽  
Malignant Progression ◽  
High Expression ◽  
Invasion And Migration ◽  
Cytoskeleton Remodeling ◽  
And Migration ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is characterized by a high incidence of metastasis. The dynamic remodeling of the actin cytoskeleton plays an important role in the invasion and migration of HCC cells. In previous studies, we found that CAPZA1, a capping protein, can promote EMT of HCC cells by regulating the remodeling of the actin filament (F-actin) cytoskeleton, thus promoting the invasion and migration of HCC cells. In this study, we found that FAM21C may have a regulatory effect on CAPZA1, and we conducted an in-depth study on its potential regulatory mechanism. First, we found that FAM21C is highly expressed in HCC tissues and its high expression could promote the malignant progression of HCC. Meanwhile, the high expression of FAM21C promoted the invasion and migration of HCC cells in vitro and in vivo. Further, FAM21C interacted with CAPZA1, and their binding inhibited the capping capacity of CAPZA1, thus promoting the invasion and migration of HCC cells. This effect of FAM21C was abolished by mutating the CP-interacting (CPI) domain, the CAPZA1 binding site on FAM21C. In conclusion, high expression of FAM21C in HCC tissues can promote malignant progression of HCC and its potential mechanism involves FAM21C inhibition of CAPZA1 capping capacity by binding to CAPZA1, which drives F-actin cytoskeleton remodeling, and thus promotes invasion and migration of HCC cells.

scholarly journals Novel Synthetic Biscoumarins Target Tumor Necrosis Factor-α in Hepatocellular Carcinoma in Vitro and in Vivo

2014 ◽  
Vol 289 (46) ◽  
pp. 31879-31890 ◽  
Author(s):  
Hosadurga Kumar Keerthy ◽  
Chakrabhavi Dhananjaya Mohan ◽  
Kodappully Sivaraman Siveen ◽  
Julian E. Fuchs ◽  
Shobith Rangappa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

RSF-1/HBXAP to predict prognosis in HBV-related hepatocellular carcinoma patients after curative resection.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14538-e14538
Author(s):  
Yang Xu ◽  
Jia Fan ◽  
Robert Anders ◽  
Bin Guan ◽  
Qingfeng Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Curative Resection ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Kaplan Meier ◽  
And Migration ◽  
Proliferation And Invasion ◽  
Hcc Cells ◽  
Proliferation And Migration

e14538 Background: Remodeling and spacing factor 1(Rsf1, or HBXAP) was demonstrated consistent overexpression in several solid tumors and could be a prognostic marker, while its role in hepatocellular carcinoma (HCC) is still unclear. We try to illustrate the prognostic significance of RSF1 and its mechanism in HBV related HCC patients. Methods: RSF1 expressions were detected in tumor tissue microarrays of 254 HCC patients who underwent curative surgical resection during 2/2004 to 12/2005. Prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. The effects of RSF1 on cell proliferation and migration were tested in RSF1 knockdown and inducible HCC cells. Related genes were screened by cDNA Microarray and then confirmed by qRT-PCR and werstern blot. Results: RSF1 expression in HCC tissues was significantly related to replase of tumor in HCC patients after curative resection, and significantly related to MMP9 and HBV infection. Knockdown (or over-express) of RSF1 in HCC cells significantly inhibited (or enhanced) HCC proliferation and invasion in vitro. RSF1 controlled the expression of MMP9 in HCC cells. Conclusions: RSF1 up-regulates MMP9 and predicts poor prognosis in HBV related HCC patients after curative resection.

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