The role of microrna in the resistance to treatment of. High expression of microrna196a is associated with progression. Involvement of inflammation and its related micrornas in. Nelson hayes 1,2 and kazuaki chayama 1,2,3, 1 department of gastroenterology and metabolism, applied life sciences, institute of biomedical and health sciences, hiroshima university, 123 kasumi, minamiku, hiroshima 7348551, japan. Mirnas function as tumor suppressors or oncogenes by regulating oncogene or tumor suppressor gene expression and their related signaling pathways involved. Hepatocellular carcinoma is a type of cancer characterized by significant morbidity and high mortality rates worldwide. Role of micrornas in hepatocellular carcinoma hepatitis monthly. Furthermore, as evolutionarily conserved, nonencoding rnas, mirnas have demonstrated fundamental roles in the various. The role of mir196a in hepatocellular carcinoma hcc metastasis remains unknown. The discovery of the involvement of micrornas mirnas in hepatocarcinogenesis represents an important area of investigation for the development of their clinical applications.
Hepatocellular carcinoma hcc is one of the most common primary tumors in the world, especially in asia, africa, and southern europe, and it is the third and second major causes of cancerrelated mortality worldwide and in china, respectively. Thus, the identification of new treatment options is needed. Eligible studies were identified through multiple search strategies and assessed for relevance and. In this arena, utilities of microrna mirna as a sophisticated tool, in therapeutics and diagnostics, remains a prime focus among the leading researchers. Hepatocellular carcinoma hcc, the most common primary liver cancer, is the fifth most frequent cancer and the third cause of cancer related mortality worldwide. Since progression of chronic liver disease to hcc involves a long latency period of a few.
They are an abundant class of rna, each of which can control hundreds of gene targets and regulate diverse biological processes such as hematopoiesis, organogenesis, apoptosis and cell proliferation. These antimirs targeted mir10b, and resulted in inhibiting beast cancer metastasis to the lung but did not affect tumor growth at the site of infusion 35. Tumor suppressor microrna493 decreases cell motility and migration ability in human bladder cancer cells by downregulating rhoc and fzd4. Dipartimento di medicina sperimentale e diagnostica, universita di ferrara, via luigi borsari, 46,44121 ferrara, italy. Involvements of microrna 22 mir22 in cancer have attracted much attention, but its role in diagnosis of hepatocellular carcinoma hcc is still largely unknown. Microarray is the standard method for analyzing mirna expression profiles. Biomarkers associated with response to regorafenib in. An indepth analysis of mirnomes in human normal liver, hepatitis liver, and hepatocellular carcinoma hcc was carried out in this study. The abnormal expression of microrna5423p in hepatocellular. Hepatocellular carcinoma hcc is among the most common of solid cancers with the third highest mortality worldwide. In our indepth analysis carried out by the illumina solexa massive parallel signature sequencing, microrna99a mir. Comparison of hepatocellular carcinoma mirna expression.
Emerging role of microrna in hepatocellular carcinoma. A comprehensive analysis of cellular microrna is a benefit for early diagnosis of hepatocellular carcinoma and early clinical intervention, and microrna is considered by some to be a key target of. Massimo negrini, laura gramantieri, silvia sabbioni, carlo m. Previous studies have revealed that alterations in microrna mirna expression are a common feature of cancer. Diagnostic value of circulating micrornas for hepatocellular. Microrna99a inhibits hepatocellular carcinoma growth and. Despite improvements in hcc therapy, the prognosis for hcc patients remains poor due to a high incidence of recurrence. They found that both stat3 and its activation in ducer lif were predicted targets of mir637. Hepatocellular carcinoma hcc, the most common primary liver cancer, is the fifth most frequent cancer and the third cause of cancerrelated mortality worldwide. Hepatocellular carcinoma hcc is the third cause of cancer related death worldwide. However, the roles of mir196a and mir196b as well as mechanism in hcc progression remain poorly understood. Microrna involvement in hepatocellular carcinoma europe pmc.
Hepatocellular carcinoma hcc remains one of the most lethal forms of cancer in the world. In hcc, microrna493 suppresses hepatocellular carcinoma tumorigenesis through downregulation of anthrax toxin receptor 1 antxr1 and rspondin 2 rspo2. Curative options for hcc are limited and exclusively available for patients carrying an early stage hcc. A correction to this article has been published and is linked from the html and pdf. Hepatocellular carcinoma hcc is one of the most common cancers, leading to the second cancerrelated death in the global.
The third most highly expressed mir199ab3p is consistently. The full scale of human mirnome in specific cell or tissue, especially in cancers, remains to be determined. In a phase 3 trial resorce, regorafenib increased overall survival compared with placebo in patients with hepatocellular carcinoma hcc previously treated with sorafenib. Microrna involvement in hepatocellular carcinoma, journal of. Hepatocellular carcinoma hcc is one of the most common cancers worldwide, where it represents the third cause of cancerrelated death. Recent advances of mirna involvement in hepatocellular carcinoma and. Tp53effector micrornas in hepatocellular carcinoma hcc tp53 is a pivotal tumor suppressor gene that exerts its function by regulating the expression of target genes, as. Development of microrna therapeutics for hepatocellular. In our indepth analysis carried out by the illumina solexa massive parallel signature sequencing, microrna99a mir99a was found to be the sixth abundant microrna in the mirnome of normal human liver but was markedly downregulated in hepatocellular carcinoma hcc.
The present metaanalysis aimed to systematically evaluate the diagnostic accuracy of circulating micrornas for hcc. Microrna involvement in hepatocellular carcinoma europe. Pdf microrna involvement in hepatocellular carcinoma. And exosomal mirnas also play important roles in proliferation, invasion, metastasis, and drug resistance in hcc by regulating gene expression. Hepatocellular carcinoma hcc, which accounts for 8590% of primary liver cancer, is the fifth most common malignant tumor and the third leading cause of. Full text emerging role of micrornas in the treatment of. Chronic hepatitis b virus hbv infection is a major risk factor for hcc. Microrna493 suppresses cell proliferation and invasion by. Hepatocellular carcinoma hcc is a primary malignancy of the liver and is frequently developed in patients with hepatitis b and hepatitis c infection and advanced liver fibrosis. Involvements of microrna22 mir22 in cancer have attracted much attention, but its role in diagnosis of hepatocellular carcinoma hcc is still largely unknown.
Micrornas and hepatocellular carcinoma springerlink. Pdf the role of micrornas in hepatocellular carcinoma. Microrna involvement in hepatocellular carcinoma, journal. Micrornas as biomarkers for liver disease and hepatocellular. In humans, more than 50% of mirna genes are located at fragile sites or in. The role of micrornas mirnas in human tumorigenesis has been demonstrated by gene profiling and functional studies.
Other model studies have demonstrated success using the antimir approach in hepatocellular carcinoma 36, hodgkin lymphoma 37, neuroblastoma 38, and glioma 39. Wang y, lee at, ma jz, wang j, ren j, yang y, et al. Hepatocellular carcinoma hcc is one of the most common cancers worldwide, where it represents the third cause of cancer. Pdf the role and clinical implications of micrornas in.
The aim of the present study was carried out to investigate the association of microrna 3b mirna3b expression with the prognosis of patients with hepatocellular ca overexpression of microrna 3b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy. Micrornas mirnas are small, noncoding rnas that play an important role in posttranscriptional gene regulation and function as negative gene regulators. Cellular microrna and the tumorigenesis of hepatocellular carcinoma. Hepatocellular carcinoma hcc is the second most common cause of cancerrelated death with a limited efficacy of treatment for intermediate and advanced stages of the disease.
Hierarchical clustering of mirnas in poorly and welldifferentiated human hcc cell lines. Rna editome imbalance in hepatocellular carcinoma cancer. Tp53effector micrornas in hepatocellular carcinoma hcc tp53 is a pivotal tumor suppressor gene that exerts its function by regulating the expression of target genes, as well as noncoding genes e. Hepatocellular carcinoma hcc is one of the most common cancers worldwide and the third cause of cancerrelated death. They found that both stat3 and its activation inducer lif were predicted targets of mir637. The demoralizing outcome of hepatocellular carcinoma is mainly due to late manifestation of large tumor. Hepatocellular carcinoma hcc is one of the leading causes of cancer. Pdf hepatocellular carcinoma hcc is common and one of the most aggressive of all human cancers. Jul 17, 2014 much evidence indicates that micrornas could play potential roles as diagnostic and prognostic biomarkers of human cancers, including hepatocellular carcinoma hcc. Emerging role of micrornas in the treatment of hepatocellular.
Hcc develops through a multistep process that involves genetic and epigenetic changes. Hbvrelated hcc has poor clinical recovery because a curative treatment is still. Recent advances of mirna involvement in hepatocellular. Pdf recent advances of mirna involvement in hepatocellular. Studies in literature indicate that several hbvcoded proteins promote malignant transformation in hepatocytes 3, 4. Microrna99ainhibitshepatocellularcarcinomagrowthand. To evaluate the expression of mirna5423p in hepatocellular carcinoma, establish its function, and evaluate whether it could serve as a biomarker for diagnosis and prognosis of hcc patients. The role of microrna in the resistance to treatment of hepatocellular carcinoma muhammad yogi pratama1,2, devis pascut1, muhammad nasrum massi2, claudio tiribelli1 1fondazione italiana fegato, area science park bazovizza, trieste, italy. Recent studies have demonstrated that micrornas mirnas, a class of noncoding rnas, are aberrantly expressed. Micrornas are small rnas involved in various biological processes and cancer metastasis.
Microrna profiles in various hepatocellular carcinoma cell. In addition to genetic and epigenetic mechanisms, recent studies have shown that micrornas mirnas play essential roles in hepatocellular carcinogenesis through the post. Recent advances of mirna involvement in hepatocellular carcinoma and cholangiocarcinoma. Nelson hayes 1,2 and kazuaki chayama 1,2,3, 1 department of gastroenterology and metabolism, applied life sciences, institute of biomedical and. Jan 01, 2008 read microrna involvement in hepatocellular carcinoma, journal of cellular and molecular medicine on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Hepatocellular carcinoma hcc is the fifth most common cancer and the third leading cause of cancer related death worldwide. Although the treatment of hcc has greatly improved over the past few decades, the survival rate of patients is still quite low. Micrornas mirnas, which are a class of highly evolutionarily conserved noncoding rnas, modulate gene expression and are regulated by specific genes. Hepatocellular carcinoma hcc is a deadly disease and therapeutic efficacy in advanced hcc is limited. In an exploratory study, we analyzed plasma and tumor samples from study participants to identify genetic, microrna mirna, and protein biomarkers associated with response to regorafenib. Several therapeutic approaches such as transarterial chemoembolization tace with anthracyclines, cisplatin and multikinase inhibitor sorafenib have been appealing choices of treatments yet failed to reach a. Recent studies have indicated that mirnas, a class.
In advanced stages, traditional chemotherapy proved to be only marginally effective or even toxic. Circular rna circmto1 acts as the sponge of microrna. Reveal the important role of microrna99a in hcc development and provide prognosis predictor and therapeutic approach for hcc. To validate the regulatory relationship between mir637 and these two targets, a reporter system was used to. For this, we assembled an hcc mirna expression database using. Hcc normally develops as a consequence of underlying liver disease and is often associated with cirrhosis. Liver cancer is the fifth most common malignancy worldwide and the third leading cause of cancerassociated mortality.
Apr 15, 2019 micrornas mirnas play essential roles in progression of hepatocellular carcinoma hcc. Treatment options for hcc are very limited, as it is often diagnosed at a late stage. In recent years, advances in genome sequencing have led to the development of nextgeneration. Request pdf microrna involvement in hepatocellular carcinoma. Hepatocellular carcinoma hcc is one of the most deadly tumors, and current treatments for the disease are often ineffective. Hepatocellular carcinoma hcc is the third cause of cancerrelated death worldwide. Highly sensitive circulating microrna panel for accurate. In recent years, advances in genome sequencing have led to the development of next. Emerging role of micrornas in the treatment of hepatocellular carcinoma elisa callegari,1 marco domenicali,2 laura gramantieri,3 massimo negrini,1 silvia sabbioni4 1department of morphology, surgery and experimental medicine, university of ferrara, ferrara, 2department of medical and surgical sciences, alma mater studiorum university of bologna, 3center for applied biomedical research, s. The role of microrna in the resistance to treatment of hepatocellular carcinoma hepatocellular carcinoma hcc is the second most common cause of cancerrelated death with a limited efficacy of treatment for intermediate and advanced stages of the disease. Because of differences in risk factors, regional incidence is widely variable.
Validation of mirna prognostic power in hepatocellular carcinoma. Driver mutations involved in hcc progression were identified in the. Hepatocellular carcinoma hcc is the most common form of liver cancer and is the third leading cause of cancerrelated deaths worldwide. Poor understanding of the mechanisms underlying the pathogenesis of hcc makes it difficult to be diagnosed and treated at early stage.
Despite improvements in hcc therapy, the prognosis for hcc patients remains poor due to a. Since primary liver cancer is predominantly comprised of hcc and. Eligible studies were identified through multiple search strategies and assessed for relevance and quality. Hepatocellular carcinoma hcc is the third leading cause of cancer deaths worldwide. Development of microrna therapeutics for hepatocellular carcinoma rajagopal n. Development of microrna therapeutics for hepatocellular carcinoma. Cellular microrna and the tumorigenesis of hepatocellular. Profiling microrna expression in hepatocellular carcinoma reveals microrna224 upregulation and apoptosis inhibitor5 as a microrna224specific target. Worldwide incidence of the disease is over 600,000 cases each year 2, 3. Microrna mirna expression profiling has proven useful in diagnosing and understanding the development and progression of several diseases.
Read microrna involvement in hepatocellular carcinoma, journal of cellular and molecular medicine on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Micrornas regulate methionine adenosyltransferase 1a expression. Hepatocellular carcinoma hcc represents more than 90% of primary liver cancer, which is the fifth most prevalent cancer in the word and the third leading cause of cancerrelated mortality. Much evidence indicates that micrornas could play potential roles as diagnostic and prognostic biomarkers of human cancers, including hepatocellular carcinoma hcc. Dec 19, 2019 hepatocellular carcinoma hcc is a primary malignancy of the liver and is frequently developed in patients with hepatitis b and hepatitis c infection and advanced liver fibrosis. A number of recent studies have documented the involvement of mirnas in hcc in tumor progression and metastasis 1015. Exosomebased liquid biopsy in the management of hepatocellular carcinoma hepatoma research is an open access journal and focuses on all topics related to hepatoma. Clustering was performed according to the expression profiles of 56 differentially. Involvement of inflammation and its related micrornas in hepatocellular carcinoma ke jin1, tong li4, gonzalo sanchezduffhues3, fangfang zhou2,3, long zhang1,3 1life sciences institute and innovation center for cell signaling network, zhejiang university, hangzhou 310058, pr china.
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