scholarly journals Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Danping Huang ◽  
Bowen Yang ◽  
Yaoyao Yao ◽  
Mianmian Liao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cancer Progression ◽  
Ex Vivo ◽  
Late Phase ◽  
Critical Role ◽  
Migration And Invasion ◽  
Caveolin 1 ◽  
Proteasome Degradation ◽  
Phyllanthus Urinaria

Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated HCC). Nevertheless, its anti-metastatic action and mechanisms are not well elucidated. In this study, CP was found to exert remarkable inhibitory effects on the proliferation, migration and invasion of HBV-associated HCC cells. The following network and biological analyses predicted that CP mainly targeted Caveolin-1 (Cav-1) to induce anti-metastatic effects, and Wnt/β-catenin pathway was one of the core mechanisms of CP action against HBV-associated HCC. Further experimental validation implied that Cav-1 overexpression promoted metastasis of HBV-associated HCC by stabilizing β-catenin, while CP administration induced autophagic degradation of Cav-1, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and subsequently attenuated the metastasis-promoting effect of Cav-1. In addition, the anti-cancer and anti-metastatic action of CP was further confirmed by in vivo and ex vivo experiments. It was found that CP inhibited the tumor growth and metastasis of HBV-associated HCC in both mice liver cancer xenograft and zebrafish xenotransplantation models. Taken together, our study not only highlights the novel function of CP formula in suppressing metastasis of HBV-associated HCC, but it also addresses the critical role of Cav-1 in mediating Akt/GSK3β/β-catenin axis to control the late-phase of cancer progression.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals Relationship between IL-10 and PD-L1 in liver hepatocellular carcinoma tissue and cell lines

2020 ◽  
Author(s):  
Qian Qian ◽  
Changping Wu ◽  
Jianping Chen ◽  
Weibing Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cancer Progression ◽  
Critical Role ◽  
Clinical Importance ◽  
Interleukin 10 ◽  
Migration And Invasion ◽  
Western Blots ◽  
Expression Levels ◽  
Liver Hepatocellular Carcinoma

Abstract Background Programmed death-ligand1 (PD-L1) plays a critical role in host immunity in the setting of cancer progression. Interleukin 10 (IL-10) is a multi-cellular, multi-functional cytokine that regulates cell growth and differentiation and participates in inflammatory and immune responses. The purpose of this study was to clarify the relationship between PD-L1 and IL-10 and their clinical importance in liver hepatocellular carcinoma(LIHC).Methods LIHC patients (n=100) who underwent surgery with preoperative therapy were included in the study. By immuno-histochemical staining, PD-L1, IL-10 and CD8 positive cells were examined in resected specimens. The gene expression levels of PD-L1, IL-10 and Met were detected by qRT-PCR and Western blots, and differentially compared in cancer, adjacent and normal tissues. In cell experiments, the Bel7405 and MHCC97-H cell-lines were incubated with IL-10 or anti-IL-10 antibody, and then PD-L1 and Met expression levels were compared by ELISA and Western blots. The effect of crizotinib and/or IL-10 on the proliferation, invasion and migration of LIHC cell-lines was estimated by CCK8 and transwell assay.Results In tumor tissues, the mRNA and protein levels of PD-L1, IL-10 and Met were higher than those in adjacent tissues. The high expression levels of PD-L1 and IL-10 indicated a poor prognosis. IL-10 reduced the expression of PD-L1 in LIHC cell-lines via Met signaling pathway. Over-expression of PD-L1 in increased the levels of IL-10, and Met in in LIHC tissue and cell lines. The combination of crizotinib and IL-10 were more effective in inhibiting the proliferation, migration and invasion of LIHC cell lines. Conclusions The combination of IL-10 and PD-L1 monoclonal antibody may have therapeutic promise in treating LIHC.

miR-369-3p serves as prognostic factor and regulates cancer progression of hepatocellular carcinoma

2021 ◽  
Author(s):  
Can Chen ◽  
Yi Zong ◽  
Jiaojiao Tang ◽  
Ruisheng Ke ◽  
Lizhi Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Huh7 Cells

Background: The aim of this study was to investigate the role of miR-369-3p in hepatocellular carcinoma (HCC). Materials & methods: The expression levels of miR-369-3p were detected using the quantitative real-time reverse transcription-PCR analysis. The cell counting kit-8 and transwell assays were used to explore the effects of miR-369-3p on cell proliferation, migration and invasion of HCC cells. Results: The miR-369-3p expression was downregulated in HCC tissues and cell lines, in comparison to the normal controls, respectively. In vitro, overexpression of miR-369-3p in Hep 3B and Huh7 cells inhibited cell proliferation, migration and invasion. SOX4 was a direct target of miR-369-3p. Conclusion: Our results suggested that miR-369-3p may be a tumor suppressor in HCC by targeting SOX4.

scholarly journals MicroRNAs as Diagnostic Tools in Hepatocellular Carcinoma

2021 ◽  
Vol 3 (4) ◽  
pp. 237-246
Author(s):  
Jessica Evangelista ◽  
Elisa Zaninotto ◽  
Annalisa Gaglio ◽  
Michele Ghidini ◽  
Lucrezia Raimondi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Sample Size ◽  
Expression Patterns ◽  
Critical Role ◽  
Measurement Techniques ◽  
Small Sample ◽  
Diagnostic Tools ◽  
Migration And Invasion ◽  
Altered Expression ◽  
Liver Cancers

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

scholarly journals A Critical Role for ZDHHC2 in Metastasis and Recurrence in Human Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chuanhui Peng ◽  
Zhijun Zhang ◽  
Jian Wu ◽  
Zhen Lv ◽  
Jie Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Portal Vein ◽  
Tumor Size ◽  
Chromosomal Region ◽  
Critical Role ◽  
Migration And Invasion ◽  
Metastatic Recurrence ◽  
Tumor Thrombi

It has been demonstrated that loss of heterozygosity (LOH) was frequently observed on chromosomes 8p22-p23 in hepatocellular carcinoma (HCC) and was associated with metastasis and prognosis of HCC. However, putative genes functioning on this chromosomal region remain unknown. In this study, we evaluated LOH status of four genes on 8p22-p23 (MCPH1, TUSC3, KIAA1456, and ZDHHC2). LOH on ZDHHC2 was associated with early metastatic recurrence of HCC following liver transplantation and was correlated with tumor size and portal vein tumor thrombi. Furthermore, our results indicate that ZDHHC2 expression was frequently decreased in HCC. Overexpression of ZDHHC2 could inhibit proliferation, migration, and invasion of HCC cell line Bel-7402in vitro. These results suggest an important role for ZDHHC2 as a tumor suppressor in metastasis and recurrence of HCC.

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 LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382095702
Author(s):  
Xue-zhen Song ◽  
Xiao-ning Ren ◽  
Xiao-jun Xu ◽  
Xiao-xuan Ruan ◽  
Yi-li Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Cell Clone ◽  
Mtor Pathway ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gene Assay ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

scholarly journals LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1

2021 ◽  
Vol 11 ◽  
Author(s):  
Weidan Ji ◽  
Zhangxiao Peng ◽  
Bin Sun ◽  
Lei Chen ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Clinical Gene Therapy ◽  
First Time ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a malignant cancer with rapid proliferation and high metastasis ability. To explore the crucial genes that maintain the aggressive behaviors of cancer cells is very important for clinical gene therapy of HCC. LpCat1 was reported to be highly expressed and exert pro-tumorigenic effect in a variety of cancers, including HCC. However, its detailed molecular mechanism remained unclear. In this study, we confirmed that LpCat1 was up-regulated in HCC tissues and cancer cell lines. The overexpressed LpCat1 promoted the proliferation, migration and invasion of HCC cells, and accelerated cell cycle progression, while knocking down LpCat1 significantly inhibited cell proliferation, migration and invasion in vitro and in vivo, and arrested HCC cells at G0/G1 phase. Moreover, we proved for the first time that LpCat1 directly interacted with STAT1 which was generally recognized as a tumor suppressor in HCC. High levels of LpCat1 in HCC could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression. Conversely, down-regulation of LpCat1 would cause the opposite changes to repress the viability and motility of HCC cells. Consequently, we concluded that LpCat1 was a contributor to progression and metastasis of HCC by interacting with STAT1.

scholarly journals LncRNA CASC11 Promotes Hepatocellular Carcinoma Progression via Upregulation of UBE2T in a m6A-Dependent Manner

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Chen ◽  
Meijun Li ◽  
Liang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cancer Susceptibility ◽  
Underlying Mechanism ◽  
Epigenetic Mechanism ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Tumor Growth And Metastasis

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and the third leading cause of cancer-related deaths worldwide. Besides, it has been revealed that long non-coding RNA (LncRNA) cancer susceptibility candidate 11 (CASC11) is involved in cancer progression. However, the functional role and underlying mechanism of CASC11 in HCC remains largely unknown. In this context, here, it was found that CASC11 was upregulated in HCC tissues and associated with tumor grades, metastasis, and prognosis of HCC patients. Functionally, CASC11 facilitated HCC cell proliferation, migration, and invasion in vitro, and enhanced tumor growth and metastasis in vivo. Mechanistically, CASC11 associated with and stabilized Ubiquitin-conjugating enzyme E2T (UBE2T) mRNA. To be specific, it decreased UBE2T N6-methyladenosine (m6A) level via recruiting ALKBH5. Moreover, CASC11 inhibited the association between UBE2T mRNA and m6A reader protein YTHDF2. Taken together, our findings demonstrate the epigenetic mechanism of CASC11 in the regulation of UBE2T expression and possibly provide a novel therapeutic target for HCC treatment.

Sign in / Sign up

Export Citation Format

Share Document