scholarly journals TUG1 Is a Regulator of AFP and Serves as Prognostic Marker in Non-Hepatitis B Non-Hepatitis C Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 262 ◽  
Author(s):  
Yang-Hsiang Lin ◽  
Meng-Han Wu ◽  
Ya-Hui Huang ◽  
Chau-Ting Yeh ◽  
Kwang-Huei Lin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Expression Profiles ◽  
Survival Rates ◽  
Mrna Levels ◽  
Afp Mrna

Thyroid hormone (T3) and its receptor (TR) are involved in cell metabolism and cancer progression. Hypothyroidism is associated with significantly elevated risk of hepatocellular carcinoma (HCC). Levels of the glycoprotein alpha-fetoprotein (AFP) are increased in the majority of patients with HCC and may be useful in diagnosis and follow-up. However, the relationship between T3/TR and AFP levels in HCC is currently unclear. The expression profiles of long non-coding RNAs (lncRNAs) were compared in microarrays of HepG2-TRα1 cells treated with/without T3 and HCC specimens. The effects of T3 on taurine upregulated gene 1 (TUG1) and AFP expression were validated using qRT-PCR. A correlation between TUG1 and AFP was confirmed via RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) strategies. Finally, overall and recurrence-free survival rates were analyzed using the Kaplan–Meier method and confirmed in online datasets. T3/TR treatment reduced TUG1 expression in vitro, resulting in the downregulation of AFP mRNA. Knockdown of TUG1 suppressed cell cycle progression and soft agar colony formation and induced cellular senescence. Our data support the involvement of TUG1 in the T3/TR-mediated suppression of cell growth. AFP mRNA levels showed strong positive correlations with TUG1 and unfavorable prognosis in patients with non-hepatitis B/non-hepatitis C HCC (NBNC-HCC). T3/TR, TUG1, and AFP may potentially serve as effective prognostic markers for NBNC-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.

Disparities in Time to Treatment of Hepatocellular Carcinoma in Patients with Hepatitis B Virus versus Hepatitis C Virus

2017 ◽  
Vol 05 (03) ◽  
Author(s):  
Jennifer Wu ◽  
Tsivia Hochman ◽  
Judith D Goldberg ◽  
Jafar Al Mondhiry ◽  
Bennal Perkins ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Time To Treatment ◽  
B Virus ◽  
Virus Versus

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 Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
JiangSheng Zhao ◽  
GuoFeng Chen ◽  
Jingqi Li ◽  
Shiqi Liu ◽  
Quan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle Progression ◽  
Lung Metastases ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
And Migration ◽  
Healthy Liver

Abstract Background PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. Methods PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. Results PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. Conclusions This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

scholarly journals YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

2021 ◽  
Vol 22 (13) ◽  
pp. 7226
Author(s):  
Violeta Stojanovska ◽  
Aneri Shah ◽  
Katja Woidacki ◽  
Florence Fischer ◽  
Mario Bauer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cell Function ◽  
Trophoblast Cell ◽  
Mrna Levels ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Apoptosis And Inflammation

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.

scholarly journals Discovery of vanoxerine dihydrochloride as a CDK2/4/6 triple-inhibitor for the treatment of human hepatocellular carcinoma

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Ying Zhu ◽  
Kun-Bin Ke ◽  
Zhong-Kun Xia ◽  
Hong-Jian Li ◽  
Rong Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle Progression ◽  
G1 Arrest ◽  
Huh7 Cells ◽  
Synergistic Cytotoxicity ◽  
Combination Study ◽  
Experimental Approaches ◽  
Induced Apoptosis

Abstract Background Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC). Methods We used the combination of computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC. Results We identified vanoxerine dihydrochloride as a new CDK2/4/6 inhibitor, and a strong cytotoxicdrugin human HCC QGY7703 and Huh7 cells (IC50: 3.79 μM for QGY7703and 4.04 μM for Huh7 cells). In QGY7703 and Huh7 cells, vanoxerine dihydrochloride treatment caused G1-arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb. Drug combination study indicated that vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in vitro in Huh7 cells. Finally, in vivo study in BALB/C nude mice subcutaneously xenografted with Huh7 cells, vanoxerine dihydrochloride (40 mg/kg, i.p.) injection for 21 days produced significant anti-tumor activity (p < 0.05), which was comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in synergistic effect. Immunohistochemistry staining of the tumor tissues also revealed significantly reduced expressions of Rb and CDK2/4/6in vanoxerinedihydrochloride treatment group. Conclusions The present study isthe first report identifying a new CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrated that this drug represents a novel therapeutic strategy for HCC treatment.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Regulatory Subunit ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Normal Tissues ◽  
Hcc Cells

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P=0.019), poor differentiation (P=0.02), portal vein invasion (P<0.001), TNM stage (P=0.019), tumor metastasis (P=0.008), and recurrence (P=0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR=2.088, P=0.014) and disease-free survival (HR=2.511, P=0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P=0.0003), chemoresistance, migration (P=0.0047), and invasion (P=0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.

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.

Characteristics of Hepatitis B virus induced Hepatocellular Carcinoma in Egyptian patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Eman Mahmoud Fathy Barakat ◽  
Khalid Mahmoud AbdAlaziz ◽  
Mohamed Mahmoud Mahmoud El Tabbakh ◽  
Mohamed Kamal Alden Ali
Keyword(s):  
United States ◽  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
Hepatitis C ◽  
Hepatitis B ◽  
The United States ◽  
Age Difference ◽  
Co Morbidity ◽  
Incidence And Mortality

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as αfetoprotein at 6-month interval. Aim To compare characteristics and behavior of Hepatocellular carcinoma (HCC) in chronic HCV patients and HVB patients Patients and Methods The current study was conducted on patients with de HCC presented at HCC clinic, Tropical medicine department Ain Shams University Hospitals between December 2017 and D ecember 2018, aged (18-70 years old) . Results eline characteristics of study population shown in Table 1 at enrolment, including gender, Education status, co-morbidity, underlying presence or absence of cirrhosis, Child-Pugh class of patients infected with viral hepatitis, and alpha-fetoprotein levels. Male proportion observed to be predominant in both HCV (62%) and HBV (75.4%) infected HCC population. Overall prevalence of HCV and HBV in patients having HCC was 65.95% and 34.04%, respectively. Presence of underlying liver cirrhosis was more significantly associated with HCV seropositives as compared to HBV seropositive patients (p0.05). Table 2 shows comparison of means between HCV and HBV seropositive patients with HCC. In univariate analysis, mean age difference (11.6 years), and total bilirubin levels (-1.91mg/dl) were the only statistically significant observations noted among HCV-HCC group (p = 0.05) Conclusion Hepatocellular carcinoma is mainly caused by Hepatitis C and Hepatitis B viruses, but latter showed predominance, comparatively worldwide and correlated HBV directly as a cause of HCC rather than HCV whose relation with HCC is still unclear (Shepard et al., 2006; Di Bisceglie, 2009). Because of the geographical differences and risk factors, the epidemiological burden of HCV and HBV has been observed different in different areas of the world. In developing countries due to high burden of HCV infection as compared to HBV such as in Taiwan (HCV 17.0%, HBV 13.8%) (Kao et al., 2011), Guam (HCV 19.6%, HBV 18%) (Haddock et al., 2013), and Pakistan (HCV 4.8%, HBV 2.5%) (Rehman et al., 1996; Raza et al., 2007; Qureshi et al., 2010; Butt et al., 2012;) will possibly

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