The Molecular Pathogenesis and Clinical Implications of Hepatocellular Carcinoma

Meguro, Makoto; Mizuguchi, Toru; Kawamoto, Masaki; Hirata, Koichi

doi:10.4061/2011/818672

Cited by 20 publications

(7 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatocellular carcinoma (HCC) ranks in prevalence and mortality among the top 10 cancers all over the world. The estimated number of new cases of HCC had risen to 564, 300 and 548, 600 patients with HCC had died, representing 97.2% of persons with this diagnosis [2]. The development and progression of HCC in humans is a multi-step, long-term process, characterized by the progressive accumulation of genetic and epigenetic alterations associated with sequential evolution of morphologically distinct stages culminating in the formation of fully developed HCC.…”

Section: Introductionmentioning

confidence: 99%

Underexpression of miR-34a in Hepatocellular Carcinoma and Its Contribution towards Enhancement of Proliferating Inhibitory Effects of Agents Targeting c-MET

et al. 2013

View full text Add to dashboard Cite

Aberrant expression of microRNA-34a (miR-34a) has been reported to be involved in the tumorigenesis and progression of various classes of malignancies. However, its role in hepatocellular carcinoma (HCC) has not been completely clarified. In the current study, we have investigated the clinical significance and the in vitro contribution of miR-34a on biological functions of human HCCs. miR-34a expression in eighty-three cases of HCC formalin-fixed paraffin-embedded (FFPE) tissues decreased significantly compared to that in the adjacent liver tissues (P<0.01), as detected by real-time quantitative RT-PCR (RT-qPCR). miR-34a expression in the groups of TNM stage I and II, without metastasis and without portal vein tumor embolus, was significantly higher than that of their corresponding groups (P<0.05). In functional experiments, miR-34a mimic suppressed cell growth, migration and invasion, meanwhile it increased cellular apoptosis and caspase activity in HCC cells. miR-34a mimic also reduced phospho-ERK1/2 and phospho-stat5 signaling. In addition, miR-34a mimic enhanced the effect of cell proliferation inhibition and caspase activity induction of agents targeting c-MET (siRNAs and small molecular inhibitor su11274). In conclusion, miR-34a may act as a tumor suppressor miRNA of HCC. The strategies to increase miR-34a level might be a critical targeted therapy for HCC in future.

show abstract

Section: Introductionmentioning

confidence: 99%

Underexpression of miR-34a in Hepatocellular Carcinoma and Its Contribution towards Enhancement of Proliferating Inhibitory Effects of Agents Targeting c-MET

et al. 2013

View full text Add to dashboard Cite

show abstract

“…HCC accounts for between 85 and 90% of all cases of primary liver cancer and is the third leading cause of mortality from cancer worldwide and the fifth most common type of malignancy (1)(2)(3)(4). It has been reported that ~21,000 cases of HCC are diagnosed and ~700,000 patients succumb to the disease worldwide annually (5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

Chen

Zhao

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. is downregulated in various types of human malignancy, including hepatocellular carcinoma (HCC), renal cell carcinoma, esophageal squamous cell carcinoma, bladder cancer, ileal carcinoid and rhabdomyosarcoma. The aim of the present study was to examine the effects of miR-133a on HCC cell proliferation, colony formation, migration and invasion. miR-133a was transfected into the HCC HepG2 and SMMC-7721 cell lines and the expression levels of miR-133a were determined; in addition, cell viability assays, colony formation assays, cell migration assays, cell invasion assays, western blot analyses and luciferase assays were performed in the HCC cell lines. The results demonstrated that miR-133a significantly inhibited cell proliferation, colony formation, migration and invasion in HepG2 and SMMC-7721 cells. To the best of our knowledge, the present study also provided the first evidence that miR-133a directly downregulated the expression of matrix metallopeptidase 9 (MMP-9) in the HCC cells. In conclusion, the results of the present study indicated that miR-133a may have suppressed cell proliferation, colony formation, migration and invasion via the downregulation of MMP-9 in HCC cell lines. Therefore, MMP-9 may be used for the development of novel molecular markers and therapeutic approaches to inhibit hepatocellular carcinoma metastasis.

show abstract

“…3 The stem cell theory of cancer was first established in hematopoietic malignancies and recently extended to solid tumors including HCC. In this hierarchical model, self-renewing CSCs are at the apex and ultimately give rise to all other tumor cells.…”

Section: Commentmentioning

confidence: 99%

Stem cell geneSALL4in aggressive hepatocellular carcinoma: A cancer stem cell-specific target?

Yakaboski

Jares

2014

Hepatology

View full text Add to dashboard Cite

Background Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. Methods We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. Results SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. Conclusions SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma.

show abstract

The Molecular Pathogenesis and Clinical Implications of Hepatocellular Carcinoma

Cited by 20 publications

References 72 publications

Underexpression of miR-34a in Hepatocellular Carcinoma and Its Contribution towards Enhancement of Proliferating Inhibitory Effects of Agents Targeting c-MET

Underexpression of miR-34a in Hepatocellular Carcinoma and Its Contribution towards Enhancement of Proliferating Inhibitory Effects of Agents Targeting c-MET

MicroRNA-133a inhibits cell proliferation, colony formation ability, migration and invasion by targeting matrix metallopeptidase 9 in hepatocellular carcinoma

Stem cell geneSALL4in aggressive hepatocellular carcinoma: A cancer stem cell-specific target?

Contact Info

Product

Resources

About