scholarly journals Tumor-suppressive and tumor-promoting role of Tgf-Beta in Hepatocellular Carcinoma

2016 ◽  
Vol 9 (1) ◽  
pp. 41 ◽  
Author(s):  
Somyoth Sridurongrit
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Tumor Development ◽  
The Other ◽  
Tgf Beta ◽  
Hepatic Cells ◽  
Proliferation And Apoptosis ◽  
Regulation Of Proliferation ◽  
Metastatic Process

Tgf-Beta is a pleiotropic cytokine with diverse functions on hepatic cells. The well-known function of Tgf-Beta in pathogenesis of liver disease is to stimulate liver fibrosis that often precedes the onset of liver cancer. While Tgf-Beta-mediated fibrosis seems to make liver more prone to the development of liver cancer, Tgf-Beta suppresses initial malignant transformation of hepatic cells thru regulation of proliferation and apoptosis. On the other hand, Tgf-Beta has shown to act as an inducer of tumor development thru enhancement of metastatic process. Additionally, it has been shown that Tgf-Beta signaling in hepatocytes promotes hepatocarcinogenesis caused by certain genetic conditions. This review highlights observations that have improved an understanding of how Tgf-Beta contributes to the development of hepatocellular carcinoma.

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

scholarly journals Risk Factors Contributing to the Occurrence and Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus Patients Treated with Direct-Acting Antivirals

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 175
Author(s):  
Sara Kishta ◽  
Ashraf Tabll ◽  
Tea Omanovic Kolaric ◽  
Robert Smolic ◽  
Martina Smolic
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Dna Ploidy ◽  
Hcv Rna ◽  
Direct Acting Antivirals ◽  
Hepatic Cells ◽  
Chronic Hcv ◽  
Direct Acting

Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.

scholarly journals Immunotoxins Immunotherapy against Hepatocellular Carcinoma: A Promising Prospect

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 719
Author(s):  
Mohammad Heiat ◽  
Hamid Hashemi Yeganeh ◽  
Seyed Moayed Alavian ◽  
Ehsan Rezaie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Side Effects ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Treatment Strategy ◽  
High Efficiency ◽  
The Other ◽  
Cross Resistance ◽  
Chemotherapy Drugs ◽  
The World

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Therefore, fighting against such cancer is reasonable. Chemotherapy drugs are sometimes inefficient and often accompanied by undesirable side effects for patients. On the other hand, the emergence of chemoresistant HCC emphasizes the need for a new high-efficiency treatment strategy. Immunotoxins are armed and rigorous targeting agents that can purposefully kill cancer cells. Unlike traditional chemotherapeutics, immunotoxins because of targeted toxicity, insignificant cross-resistance, easy production, and other favorable properties can be ideal candidates against HCC. In this review, the characteristics of proper HCC-specific biomarkers for immunotoxin targeting were dissected. After that, the first to last immunotoxins developed for the treatment of liver cancer were discussed. So, by reviewing the strengths and weaknesses of these immunotoxins, we attempted to provide keynotes for designing an optimal immunotoxin against HCC.

scholarly journals Validation of mRNAs in Early Diagnosis and Treatment of Hepatocellular Carcinoma

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Iqra Khalid ◽  
Azra Quraishi ◽  
Freeha Fiaz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Early Stage ◽  
Therapeutic Targets ◽  
Minimal Invasive ◽  
Detection Methods ◽  
Circulating Micrornas ◽  
Novel Biomarkers ◽  
Diseased State

Poor and late diagnosis of HCV is main the cause of liver cancer. MicroRNAs are non-coding molecules that are involved in regulation of a variety of functions happening in the cell, in healthy and diseased state. Dysregulation of microRNAs is observed in different diseases, especially in liver cancer like hepatocellular carcinoma. The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for diagnosis at an earlier stage to minimize chances of liver cancer. Circulating microRNAs are novel and minimal invasive markers for early detection of HCV based hepatocellular carcinoma. In this review, the current progress on the potential role of miRNA as biomarkers for detection of HCC and therapeutic targets are summarized. We concluded that the expression of microRNAis upregulated in the patients of hepatocellular carcinoma when compared with the healthy ones. In-depth studies of miRNA in patients of HCC as genetic biomarkers will improve the diagnosis. It will also improve the prognosis of early stage HCC patients. This will also help in identifying a suitable and effective therapeutic targets so as to reduce the chances of failure of chemotherapy.

scholarly journals RhoGTPase Signalling in Cancer Progression and Dissemination

2021 ◽  
Author(s):  
Eva Crosas-Molist ◽  
Remi Samain ◽  
Leonie Kohlhammer ◽  
Jose Orgaz ◽  
Samantha George ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Tumour Microenvironment ◽  
Normal Tissues ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Metastatic Process ◽  
Tumour Initiation

Rho GTPases are a family of small G proteins that regulate a wide array of cellular processes related to their key roles controlling the cytoskeleton. On the other hand, cancer is a multi-step disease caused by the accumulation of genetic mutations and epigenetic alterations, from the initial stages of cancer development when cells in normal tissues undergo transformation, to the acquisition of invasive and metastatic traits, responsible for a large number of cancer related deaths. In this review, we discuss the role of Rho GTPase signalling in cancer in every step of disease progression. Rho GTPases contribute to tumour initiation and progression, by regulating proliferation and apoptosis, but also metabolism, senescence and cell stemness. Rho GTPases play a major role in cell migration, and in the metastatic process. They are also involved in interactions with the tumour microenvironment and regulate inflammation, contributing to cancer progression. After years of intensive research, we highlight the importance of relevant models in the Rho GTPase field, and we reflect on the therapeutic opportunities arising for cancer patients.

scholarly journals MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4

2020 ◽  
Author(s):  
Ji Lin ◽  
Huijuan Huang ◽  
Liheng Lin ◽  
Weiwei Li ◽  
Jianfen Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Regulation Of Proliferation ◽  
Healthy Control

Abstract Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

scholarly journals NTF3 Correlates With Prognosis and Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Rongqiang Liu ◽  
Rongqi Li ◽  
Haoyuan Yu ◽  
Jianrong Liu ◽  
Shiyang Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Prognostic Factor ◽  
Liver Cancer ◽  
Potential Role ◽  
Immune Checkpoints ◽  
Cd4 Cells ◽  
Clinical Value ◽  
Immune Infiltration

Background: The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC).Methods: We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics.Results: NTF3 was low expressed in HCC and was an independent prognostic factor in patients with HCC. CIBERSORT analysis indicated that NTF3 expression was positively correlated with CD4+ cells, mast cells, NK cells, macrophages and B cells in the tumor microenvironment. Furthermore, we found that NTF3 expression was negatively correlated with the immune checkpoints PD-L1, TIGIT and TIM-3. Functional network analysis revealed that NTF3 regulates HCC progression through a variety of cancer-related kinases, transcription factors and signaling pathways.Conclusions: We demonstrate that NTF3 correlates with prognosis and immune infiltration in HCC.

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