The Role of Serum microRNA (hsa-miR-519d) And the Associated Target Gene (SQSTM1) As Diagnostic Biological Molecular Biomarkers for Hepatocellular Carcinoma

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Mohamed Youssef ◽  
Wesam Ahmed Ibrahim ◽  
Sarah Abdel Kader El Nakeep ◽  
Amina Ahmed Mahmoud Swilam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Sensitivity And Specificity ◽  
Messenger Rna ◽  
Target Gene ◽  
Molecular Biomarkers ◽  
Chronic Liver ◽  
Transcriptional Level ◽  
Serum Microrna ◽  
Liver Infection

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver cancer. The mortality of liver cancer worldwide is ranked as fourth between other cancer causes in males and females. In Egypt, it is a major problem due to the high prevalence of Hepatitis C Virus infection. Objective To characterize the expression of new serum non-coding RNA microRNA (hsa-miR519d) and the associated target gene (SQSTM1) to evaluate their usefulness as diagnostic molecular biomarkers for HCC. Patients and Methods we assessed the expression of the microRNA (hsa-miR-519d-3p) and the mRNA of (SQSTM1) gene in serum samples from 50 participants: (34) HCC patients, (11) chronic liver infection patients and (5) normal volunteers, using Quantitative Real Time Polymerase Chain Reaction (qPCR). Results The results of both microRNA (miR-519d-3p) and mRNA of (SQSTM1) gene showed a significant upregulation of their serum level in the HCC group in comparison to chronic liver infection group. In addition, the results of the serum microRNA (miR-519d) and the messenger RNA of (SQSTM1) gene using receiver operating characteristic (ROC) curve showed higher sensitivity and specificity than that of AFP, as it was (91.2%-81.8%), (97.1%-100%) and (76.5%72.7%) respectively. Conclusion The serum microRNA (hsa-mir-519d-3p) and the serum mRNA of its targeted gene (SQSTM1) are both significantly upregulated in the serum of Hepatocellular carcinoma (HCC) patients. And that the (hsa-mir-519d-3p) stimulates the gene (SQSTM1) at the transcriptional level. Finally, we could conclude that the serum microRNA (hsa-mir-519d-3p) and the serum mRNA of (SQSTM1) gene can be used as diagnostic biomarkers for HCC with good sensitivity and specificity even for early stages of HCC in comparison with AFP.

scholarly journals The impact of endotrophin on the progression of chronic liver disease

2020 ◽  
Vol 52 (10) ◽  
pp. 1766-1776
Author(s):  
Min Kim ◽  
Changhu Lee ◽  
Dae Yun Seo ◽  
Hyojung Lee ◽  
Jay D. Horton ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Liver Cancer ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Hepatic Inflammation ◽  
Fibrotic Liver ◽  
Alcoholic Fatty Liver ◽  
The Impact

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The fibrotic liver is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Type VI collagen alpha3 (Col6a3) is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Here, we studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer. We used a doxycycline (Dox)-inducible liver-specific ETP-overexpressing mouse model on a NAFLD-prone (liver-specific SREBP1a transgenic) background. For this, we evaluated the consequences of local ETP expression in the liver and its effect on hepatic inflammation, fibrosis, and insulin resistance. Accumulation of ETP in the liver induced hepatic inflammation and the development of fibrosis with associated insulin resistance. Surprisingly, ETP overexpression also led to the emergence of liver cancer within 10 months in the SREBP1a transgenic background. Our data revealed that ETP can act as a “second hit” during the progression of NAFLD and can play an important role in the development of NASH and hepatocellular carcinoma (HCC). These observations firmly link elevated levels of ETP to chronic liver disease.

scholarly journals The Alpha-fetoprotein Serum is still Reliable as a Biomarker for the Surveillance of Hepatocellular Carcinoma in Indonesia

2020 ◽  
Author(s):  
Chyntia Olivia Maurine Jasirwan ◽  
Alessa - Fahira ◽  
Lianda - Siregar ◽  
Imelda - Loho
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Cross Sectional Study ◽  
Surveillance Program ◽  
Average Life Expectancy ◽  
Cross Sectional ◽  
Patients At Risk

Abstract Background and Aims: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is one of the leading causes of cancer-related death worldwide with an inferior prognosis. In Indonesia, the average life expectancy is less than 3 months, with most patients being in an advanced stage where in the survival rate is very low. Early detection through surveillance program is very crucial. HCC guidelines worldwide have provided surveillance recommendation through the examination of α-fetoprotein (AFP) and ultrasound for patients at risk in developing HCC. However, there have been some controversies regarding the usage of AFP concerning its low sensitivity and specificity in detecting HCC. Therefore, the effectiveness of AFP in the surveillance of HCC patients and identifying the parameters most associated with the increase of AFP≥10 ng/ml in Indonesia should be evaluated.Methods: We analysed medical records of HCC patients and those at high-risk of developing HCC through cross-sectional study, including patients with cirrhosis and hepatitis B and C, from 2015 to 2017 who underwent treatment at the Cipto Mangunkusumo National Hospital and Dharmais National Cancer Hospital, Indonesia.Results: The sensitivity and specificity of AFP in the surveillance of HCC in Indonesia with a cut-off of 10 ng/ml were 82.6% and 68.9%, respectively. The parameters most associated with the increase of AFP ≥10 ng/ml according to multivariate analysis were the etiology of hepatitis B, the stage of Barcelona Clinic Liver Cancer B and C, and the presence of cirrhosis, respectively.Conclusion: AFP can still be used in the surveillance of HCC in Indonesia for its high sensitivity value.

scholarly journals TUG1 Promotes the Expression of IFITM3 in Hepatocellular Carcinoma by Competitively Binding to miR-29a

2020 ◽  
Author(s):  
Qian Feng ◽  
Weiwei Liu ◽  
Wenjun Liao ◽  
Jun Gao ◽  
Jiyuan Ai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Human Liver ◽  
Target Gene ◽  
Liver Cancer Cells ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Background: Numerous studies have demonstrated the important relationship of TUG1 with tumorigenesis. The present study investigated the role of TUG1 and its downstream genes miR-29a and IFITM3 in the occurrence and development of hepatocellular carcinoma (HCC). We found that both TUG1 and IFITM3 genes are highly expressed in HCC, whereas the expression of miR-29a is low in HCC. Downregulation of TUG1 reduces cell invasion, metastasis, and cell proliferation ability and promotes cell apoptosis. Simultaneous downregulation of miR-29a reverses this effect. Moreover, IFITM3, as the target gene of miR-29a, is positively regulated by TUG1. However, the adjustment relationship between these three components is still unknown and thus warrants further investigation. The present study investigated the regulatory relationship between TUG1, miR-29a, and IFITM3 in human liver cancer.Methods: The expression of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 65 patients with HCC was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The migration and invasion of liver cancer cells were studied by the wound healing assay and the Transwell method, respectively. The apoptosis rate of HCC cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the 5-ethynyl-2′-deoxyuridine (EDU) method. Immunofluorescence was used to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702 cell lines. The relationship between TUG1 and miR-29a was detected using a double luciferase reporter assay and fluorescence in situ hybridization (FISH). Tumors were established in vivo by subcutaneous injection of HCC cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers.Results: The expression of TUG1 increased significantly in tumor tissues and HCC cells. Moreover, the expression of miR-29a in liver cancer tissues was significantly lower than that in normal human liver tissues. The expression of TUG1 in liver cancer tissue was negatively correlated with miR-29a. Knockdown of TUG1 weakened the invasion, migration, and proliferation of HCC cells, and enhanced their apoptosis. A simultaneous knockdown of miR-29a enhanced cell invasion, metastasis, and cell proliferation, whereas the apoptosis ability decreased. As a target gene of miR-29a, IFITM3 is not only negatively regulated by miR-29a, but also positively regulated by TUG1. Therefore, TUG1 regulates IFITM3 in HCC cells by competitively binding to miR-29a, thus affecting cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds to miR-29a to regulate IFITM3 and promote the development of liver cancer. Downregulation of TUG1 can significantly inhibit the migration, invasion, and proliferation of liver cancer cells. Based on these results, we conclude that TUG1 could serve as a key gene to improve the prognosis of patients with HCC.

scholarly journals The Alpha-fetoprotein Serum is still Reliable as a Biomarker for the Surveillance of Hepatocellular Carcinoma in Indonesia

2020 ◽  
Author(s):  
Chyntia Olivia Maurine Jasirwan ◽  
Alessa - Fahira ◽  
Lianda - Siregar ◽  
Imelda - Loho
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Sensitivity And Specificity ◽  
High Sensitivity ◽  
Cross Sectional Study ◽  
Surveillance Program ◽  
Average Life Expectancy ◽  
Cross Sectional ◽  
Patients At Risk

Abstract Background and Aims Hepatocellular carcinoma (HCC), the most common type of liver cancer, is one of the leading causes of cancer-related death worldwide with an inferior prognosis. In Indonesia, the average life expectancy is less than 5 months, with most patients being in an advanced stage wherein the survival rate is very low. Early detection through surveillance program is very crucial. HCC guidelines worldwide have provided surveillance recommendation through the examination of α-fetoprotein (AFP) and ultrasound for patients at risk in developing HCC. However, there have been some controversies regarding the usage of AFP concerning its low sensitivity and specificity in detecting HCC. Therefore, the effectiveness of AFP in the surveillance of HCC patients and identifying the parameters most associated with the increase of AFP≥10 ng/ml in Indonesia should be evaluated. Methods We analyzed medical records of HCC patients and those at high risk of developing HCC through cross-sectional study, including patients with cirrhosis and hepatitis B and C, from 2015 to 2017 who underwent treatment at the Cipto Mangunkusumo National Hospital and Dharmais National Cancer Hospital, Indonesia. Results The sensitivity and specificity of AFP in the surveillance of HCC in Indonesia with a cut-off of 10 ng/ml were 82.6% and 71.2%, respectively. The parameters most associated with the increase of AFP ≥10 ng/ml according to multivariate analysis were the etiology of hepatitis B, the stage of Barcelona Clinic Liver Cancer B and C, and the presence of cirrhosis, respectively. Conclusion AFP can still be used in the surveillance of HCC in Indonesia for its high sensitivity value.

An Overview of Natural Plant Products in the Treatment of Hepatocellular Carcinoma

2019 ◽  
Vol 18 (13) ◽  
pp. 1838-1859 ◽  
Author(s):  
Divya Rawat ◽  
Somi Shrivastava ◽  
Rayees A. Naik ◽  
Saurabh K. Chhonker ◽  
Aditi Mehrotra ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Herbal Medicines ◽  
Incidence Rates ◽  
Chronic Liver ◽  
Chronic Infections ◽  
Natural Plant ◽  
Plant Products ◽  
Liver Cancers

Background: Liver cancer is the fifth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Among the liver cancers, hepatocellular carcinoma has been reported to be responsible for 85-90% of primary liver cancer and it is the second most common cause of cancer mortality with 700,000 deaths documented annually. The major risk factors of HCC include chronic infections with the hepatitis B (HBV) or hepatitis C (HCV) virus, chronic liver diseases, alcoholism as well as dietary carcinogens, such as aflatoxins. Highest incidence rates are estimated to occur in Asia and Africa. Objective: The effectiveness of current man-made agents in treating chronic liver disease is not satisfactory and they have uninvited side effects. Herbal medicines are extensively used all over the world; however, there is still a vast gap in their acceptance by the scientific community. Plants are rich in secondary metabolites and phytochemicals obtained from both, dietary and non-dietary sources. Natural plant products are potent therapeutic as well as chemopreventive agents for numerous chronic diseases like cardiovascular, metabolic, neurodegenerative and neoplastic diseases. Results: Dietary phytochemicals such as curcumin, resveratrol, quercetin, silibinin, N-trans-feruloyl octopamine, lycopene, emodin, caffeine, urolithin A and Phloretin have been found to be useful for the treatment of HCC and other diseases. According to recent reports 60% of the anticancer medication in current use has been obtained from natural sources. Conclusion: Thus, derivatives from plants have played an essential role in cancer prevention due to their pleiotropic abilities to scavenge free radicals, inhibit cell growth and induce apoptosis.

scholarly journals Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma

Gut ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1676-1687 ◽  
Author(s):  
Mateus T Guerra ◽  
Rodrigo M Florentino ◽  
Andressa Franca ◽  
Antonio C Lima Filho ◽  
Marcone L dos Santos ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Liver Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Chronic Liver Disease ◽  
De Novo ◽  
Chronic Liver ◽  
Liver Cancer Cells ◽  
Type 3

Background & objectivesHepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide. Several types of chronic liver disease predispose to HCC, and several different signalling pathways have been implicated in its pathogenesis, but no common molecular event has been identified. Ca2+ signalling regulates the proliferation of both normal hepatocytes and liver cancer cells, so we investigated the role of intracellular Ca2+ release channels in HCC.DesignExpression analyses of the type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR3) in human liver samples, liver cancer cells and mouse liver were combined with an evaluation of DNA methylation profiles of ITPR3 promoter in HCC and characterisation of the effects of ITPR3 expression on cellular proliferation and apoptosis. The effects of de novo ITPR3 expression on hepatocyte calcium signalling and liver growth were evaluated in mice.ResultsITPR3 was absent or expressed in low amounts in hepatocytes from normal liver, but was expressed in HCC specimens from three independent patient cohorts, regardless of the underlying cause of chronic liver disease, and its increased expression level was associated with poorer survival. The ITPR3 gene was heavily methylated in control liver specimens but was demethylated at multiple sites in specimens of patient with HCC. Administration of a demethylating agent in a mouse model resulted in ITPR3 expression in discrete areas of the liver, and Ca2+ signalling was enhanced in these regions. In addition, cell proliferation and liver regeneration were enhanced in the mouse model, and deletion of ITPR3 from human HCC cells enhanced apoptosis.ConclusionsThese results provide evidence that de novo expression of ITPR3 typically occurs in HCC and may play a role in its pathogenesis.

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