Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Molecular Mechanisms of Hepatocellular Carcinoma
share announcement

Molecular Mechanisms of Hepatocellular Carcinoma

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Proliferation and Division".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 22558

Special Issue Editors

Dr. Kyu Yun Jang

E-Mail Website
Guest Editor
Department of Pathology, Jeonbuk National University Medical School, 567 Baekje-daero, Dukjin-gu, Jeonju 54896, Korea
Interests: cancer progression; sirtuins; DNA damage repair; cytokines and cytokine receptors; hormone receptors; anti-cancer immunity; epithelial-to-mesenchymal transition; cell death; osteosarcoma; bone regeneration
Dr. See-Hyoung Park

E-Mail Website
Guest Editor
Department of Biological and Chemical, Hongik University, Sejong, Republic of Korea
Interests: natural compounds; chemical genomics; functional foods; cosmeceuticals; cancer biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCC is often diagnosed at an advanced stage and has a very poor prognosis. HCC has the phenotypical and genetical heterogenicity resultant from chronic liver disease. The curative therapies against HCC are resection, transplantation, and trans-arterial interventions, which show very limited efficacy. It is also hard to cure HCC with standard chemotherapy and radiotherapy. Thus, we still need to understand how signaling pathways and molecular alterations play essential roles in HCC development, which could help develop effective therapeutic options against HCC. In this Special Issue, we will gather manuscripts handling the novel signaling pathway, the new potential therapeutic targets, and the clinically proven novel targets in HCC biology.

Dr. Kyu Yun Jang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatocellular carcinoma
  • oncogene
  • apoptosis
  • signaling pathway
  • therapeutics
  • target

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 10105 KiB  
Article
CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated β-Catenin Pathway
by Yong Qi, Haibo Wang, Qikun Zhang, Zhiqiang Liu, Tianbing Wang, Zhengsheng Wu and Wenyong Wu
Cells 2022, 11(23), 3857; https://doi.org/10.3390/cells11233857 - 30 Nov 2022
Cited by 12 | Viewed by 2127
Abstract
Currently, exosomes derived from Cancer-associated fibroblast (CAF) have reportedly been involved in regulating hepatocellular carcinoma (HCC) tumour microenvironment (TME). LIM domain and actin binding 1 (LIMA1) is an actin-binding protein that is involved in controlling the biological behaviour and progression of specific solid [...] Read more.
Currently, exosomes derived from Cancer-associated fibroblast (CAF) have reportedly been involved in regulating hepatocellular carcinoma (HCC) tumour microenvironment (TME). LIM domain and actin binding 1 (LIMA1) is an actin-binding protein that is involved in controlling the biological behaviour and progression of specific solid tumours. We aimed to determine the effect of LIMA1 and exosome-associated miR-20a-5p in HCC development. LIMA1 and miR-20a-5p expression levels were examined by real-time quantitative PCR (qRT-PCR), western blotting or immunohistochemistry (IHC). Functional experiments, including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) assays, colony formation assays, wound healing assays, and Transwell invasion assays, were performed to investigate the effect of LIMA1 and miR-20a-5p. A dual-luciferase reporter gene assay was performed to confirm the interaction of miR-20a-5p and LIMA1. Exosomes were characterised by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. We noted that LIMA1 was downregulated in human HCC tissues and cells and remarkably correlated with overall survival (OS) and recurrence-free survival (RFS). LIMA1 overexpression suppressed HCC cell proliferation and metastasis in vitro and in vivo, while LIMA1 knockdown had the opposite effects. A mechanistic investigation showed that LIMA1 inhibited the Wnt/β-catenin signalling pathway by binding to BMI1 and inducing its destabilisation. Additionally, we found that LIMA1 expression in HCC cells could be suppressed by transferring CAF-derived exosomes harbouring oncogenic miR-20a-5p. In summary, LIMA1 is a tumour suppressor that inhibits the Wnt/β-catenin signalling pathway and is downregulated by CAF-derived exosomes carrying oncogenic miR-20a-5p in HCC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Graphical abstract

12 pages, 1901 KiB  
Article
Upregulation of USP22 and ABCC1 during Sorafenib Treatment of Hepatocellular Carcinoma Contribute to Development of Resistance
by Yung-Sheng Chang, Chien-Wei Su, San-Chi Chen, Yen-Ying Chen, Yuh-Jin Liang and Jaw-Ching Wu
Cells 2022, 11(4), 634; https://doi.org/10.3390/cells11040634 - 11 Feb 2022
Cited by 13 | Viewed by 2165
Abstract
Sorafenib is a small molecule that blocks tumor proliferation by targeting the activity of multi-kinases for the treatment of advanced hepatocellular carcinoma (HCC). Increasing sorafenib resistance following long-term treatment is frequently encountered. Mechanisms underlying sorafenib resistance remain not completely clear. To further understand [...] Read more.
Sorafenib is a small molecule that blocks tumor proliferation by targeting the activity of multi-kinases for the treatment of advanced hepatocellular carcinoma (HCC). Increasing sorafenib resistance following long-term treatment is frequently encountered. Mechanisms underlying sorafenib resistance remain not completely clear. To further understand the mechanism of sorafenib resistance in HCC, we established sorafenib-resistant cell lines by slowly increasing sorafenib concentration in cell culture medium. Upregulation of USP22 and ABCC1 were found in Sorafenib-resistant cells. Sorafenib-resistant cells treated with USP22 siRNA showed significant reduction in endogenous mRNA and protein levels of ABCC1. During sorafenib treatment, upregulation of USP22 increases ABCC1 expression and subsequently contributes to sorafenib resistance in HCC cells. Immunohistochemical analysis revealed a positive correlation between USP22 and ABCC1 expression in tissue samples from sorafenib-resistant patients (Pearson’s correlation = 0.59, p = 0.03). Our findings indicate that upregulation of USP22 and ABCC1 expression during treatment contribute to sorafenib resistance in HCC cells and that USP22 has strong potential as a therapeutic target for overcoming sorafenib resistance in HCC patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Figure 1

10 pages, 1716 KiB  
Article
Accumulation of Genetic and Epigenetic Alterations in the Background Liver and Emergence of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease
by Satoru Hagiwara, Naoshi Nishida, Kazuomi Ueshima, Yasunori Minami, Yoriaki Komeda, Tomoko Aoki, Masahiro Takita, Masahiro Morita, Hirokazu Chishina, Akihiro Yoshida, Hiroshi Ida and Masatoshi Kudo
Cells 2021, 10(11), 3257; https://doi.org/10.3390/cells10113257 - 21 Nov 2021
Cited by 6 | Viewed by 2133
Abstract
The incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We analyzed 16 surgically resected HCC cases in which the background liver was pathologically diagnosed as NAFLD. Specimens with Brunt classification grade 3 or higher were assigned [...] Read more.
The incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We analyzed 16 surgically resected HCC cases in which the background liver was pathologically diagnosed as NAFLD. Specimens with Brunt classification grade 3 or higher were assigned as the fibrotic progression group (n = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (n = 8). Comprehensive mutational and methylome analysis was performed in cancerous and noncancerous tissues. The target gene mutation analysis with deep sequencing revealed that CTNNB1 and TP53 mutation was observed in 37.5% and TERT promoter mutation was detected in 50% of cancerous samples. Furthermore, somatic mutations in non-cancerous samples were less frequent, but were observed regardless of the progression of fibrosis. Similarly, on cluster analysis of methylome data, status for methylation events involving non-cancerous liver was similar regardless of the progression of fibrosis. It was found that, even in cases of non-progressive fibrosis, accumulation of gene mutations and abnormal methylation within non-cancerous areas were observed. Patients with NAFLD require a rigorous liver cancer surveillance due to the high risk of HCC emergence based on the accumulation of genetic and epigenetic abnormalities, even when fibrosis is not advanced. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Figure 1

12 pages, 2062 KiB  
Article
Eg5 as a Prognostic Biomarker and Potential Therapeutic Target for Hepatocellular Carcinoma
by Yu-Yun Shao, Nai-Yun Sun, Yung-Ming Jeng, Yao-Ming Wu, Chiun Hsu, Chih-Hung Hsu, Hey-Chi Hsu, Ann-Lii Cheng and Zhong-Zhe Lin
Cells 2021, 10(7), 1698; https://doi.org/10.3390/cells10071698 - 05 Jul 2021
Cited by 5 | Viewed by 2088
Abstract
Background: The kinesin Eg5, a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of Eg5 in hepatocellular carcinoma (HCC). Methods: HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. Eg5 [...] Read more.
Background: The kinesin Eg5, a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of Eg5 in hepatocellular carcinoma (HCC). Methods: HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. Eg5 expression levels were correlated with overall survival (OS) and disease-free survival (DFS). In vitro efficacy of LGI-147, a specific Eg5 inhibitor, was tested in HCC cell lines. In vivo efficacy of Eg5 inhibition was investigated in a xenograft model. Results: A total of 108 HCC samples were included. The patients were divided into three tertile groups with high, medium, and low Eg5 expression levels. OS of patients with low Eg5 expression was better than that of patients with medium and high Eg5 expression (median, 155.6 vs. 75.3 vs. 57.7 months, p = 0.002). DFS of patients with low Eg5 expression was also better than that of patients with medium and high Eg5 expression (median, 126.3 vs. 46.2 vs. 39.4 months, p = 0.001). In multivariate analyses, the associations between Eg5 expression and OS (p < 0.001) or DFS remained (p < 0.001). LGI-147 reduced cell growth via cell cycle arrest and apoptosis and induced accumulation of abnormal mitotic cells. In the xenograft model, the tumor growth rate under LGI-147 treatment was significantly slower than under the control. Conclusion: High Eg5 expression was associated with poor HCC prognosis. In vitro and in vivo evidence suggests that Eg5 may be a reasonable therapeutic target for HCC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Figure 1

Review

Jump to: Research

23 pages, 1412 KiB  
Review
Hepatitis B Viral Protein HBx and the Molecular Mechanisms Modulating the Hallmarks of Hepatocellular Carcinoma: A Comprehensive Review
by Enakshi Sivasudhan, Neil Blake, Zhiliang Lu, Jia Meng and Rong Rong
Cells 2022, 11(4), 741; https://doi.org/10.3390/cells11040741 - 21 Feb 2022
Cited by 24 | Viewed by 7176
Abstract
With 296 million cases estimated worldwide, chronic hepatitis B virus (HBV) infection is the most common risk factor for hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key multifunctional regulatory protein, drives viral replication and interferes with several cellular signalling pathways that [...] Read more.
With 296 million cases estimated worldwide, chronic hepatitis B virus (HBV) infection is the most common risk factor for hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key multifunctional regulatory protein, drives viral replication and interferes with several cellular signalling pathways that drive virus-associated hepatocarcinogenesis. This review article provides a comprehensive overview of the role of HBx in modulating the various hallmarks of HCC by supporting tumour initiation, progression, invasion and metastasis. Understanding HBx-mediated dimensions of complexity in driving liver malignancies could provide the key to unlocking novel and repurposed combinatorial therapies to combat HCC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Graphical abstract

26 pages, 5016 KiB  
Review
The Translational Bridge between Inflammation and Hepatocarcinogenesis
by Sabine Gufler, Rita Seeboeck, Christoph Schatz and Johannes Haybaeck
Cells 2022, 11(3), 533; https://doi.org/10.3390/cells11030533 - 03 Feb 2022
Cited by 9 | Viewed by 2744
Abstract
Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, [...] Read more.
Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, alcoholic- and non-alcoholic steatohepatitis, and autoimmune hepatitis, and highlight their driving mechanisms. These include external factors such as alcohol misuse, viral infection and supernutrition, as well as intrinsic parameters such as genetic disposition and failure, in immune tolerance. Additionally, we describe what is known about the translational machinery within all these diseases. Distinct eukaryotic translation initiation factors (eIFs) with specific functional roles and aberrant expression in HCC are reported. Many alterations to the translational machinery are already triggered in the precancerous lesions described in this review, highlighting mTOR pathway proteins and eIFs to emphasize their putative clinical relevance. Here, we identified a lack of knowledge regarding the roles of single eIF proteins. A closer investigation will help to understand and treat HCC as well as the antecedent diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Figure 1

21 pages, 1240 KiB  
Review
The Role of Immunotherapy in a Tolerogenic Environment: Current and Future Perspectives for Hepatocellular Carcinoma
by Liliana Montella, Federica Sarno, Annamaria Ambrosino, Sergio Facchini, Maria D’Antò, Maria Maddalena Laterza, Morena Fasano, Ermelinda Quarata, Raffaele Angelo Nicola Ranucci, Lucia Altucci, Massimiliano Berretta and Gaetano Facchini
Cells 2021, 10(8), 1909; https://doi.org/10.3390/cells10081909 - 27 Jul 2021
Cited by 12 | Viewed by 2898
Abstract
In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The [...] Read more.
In contrast to several tumors whose prognoses are radically affected by novel immunotherapeutic approaches and/or targeted therapies, the outcomes of advanced hepatocellular carcinoma (HCC) remain poor. The underlying cirrhosis that is frequently associated with it complicates medical treatment and often determines survival. The landscape of HCC treatment had included sorafenib as the only drug available for ten years, until 2018, when lenvatinib was approved for treatment. The second-line systemic treatments available for hepatocellular carcinoma include regorafenib, cabozantinib, ramucirumab, and, more recently, immune checkpoint inhibitors. However, the median survival remains below 15 months. The results obtained in clinics should be interpreted whilst considering the peculiar role of the liver as an immune organ. A healthy liver microenvironment ordinarily experiences stimulation by gut-derived antigens. This setup elucidates the response to chronic inflammation and the altered balance between tolerance and immune response in HCC development. This paper provides an overview of the mechanisms involved in HCC pathogenesis, with a special focus on the immune implications, along with current and future clinical perspectives. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Hepatocellular Carcinoma)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop