Relation between microRNAs and Apoptosis in Hepatocellular Carcinoma

Kamel, Rabab; Amr, Khalda; Afify, Mie; Elhosary, Yasser A.; Hegazy, Abdelfattah E.; Fahim, Hoda H.; Ezzat, Wafaa M.

doi:10.3889/oamjms.2016.038

Cited by 17 publications

(20 citation statements)

References 27 publications

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“…17,33 Different studies revealed the different roles of miRNAs in cancer growth through apoptosis. 25 Our study results confirm that miR-196a is mostly involved in the early stage of cell death in Huh 7.5 cells. Further research is suggested to better understand the effect of miR-196a on the pathway of cell death.…”

Section: Discussionsupporting

confidence: 80%

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Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors

Shafaati

Jamalidoust

Kargar

et al. 2021

Microbiology and Immunology

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Hepatitis C virus (HCV) is a positive-sense, single-stranded RNA virus that causes chronic hepatitis and hepatocellular carcinoma. Cellular microRNAs (miRNAs) directly modulate the viral infectivity and indirectly through targeting virus-related host factors. They play an essential role in the progression of different stages of HCV infection. The roles of miR-196 family in HCV infection and hepatocellular carcinoma progression remain poorly understood. Using ViTa databases, miR-196a as a high-score miRNA targeting the NS 5 A region of HCV genome was selected. Using dual luciferase assay and an established cell-cultured HCV (HCVcc) system, the effect of miR-196a on HCV genome was assessed. In silico analysis demonstrated the significant role of miR-196a in the downregulation of HCV replication. Using dual luciferase assay, the liver-specific miR-196a and NS 5 A gene binding was confirmed. To assess the experimental role of miR-196a, an HCVcc system was established in the Huh 7.5 cell lines. The HCV-RNA 1b derived from an infected patient was transfected into Huh 7.5 cells containing miR-196a lentiviral vectors (Huh 7.5/miR-196a), mocks (Huh 7.5/mock vector), and naïve Huh 7.5 cells. The rate of reduction of the HCV genome replication was assessed using relative real-time PCR assay. These results represent miR-196a overexpression and its roles in regulating HCV genome replication. However, miR-196a may inhibit HCV replication and accelerate the early stages of apoptosis. Overexpression of miR-196a in Huh 7.5 replicon cell is a potential new strategy to prevent hepatitis C infection. The results of this study suggest that miR-196a directly downregulates HCV replication and may serve as a new antiviral therapy.

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Section: Discussionsupporting

confidence: 80%

“…The cells were inoculated with serum containing 10 5 HCV-RNA copies prepared from an HCVpositive blood. 25 The cells were plated in 10% DMEM and then passaged every 2-4 days. Using real-time PCR assay, the titer of progeny viruses was assessed.…”

Section: Hcv-rna Transfectionmentioning

confidence: 99%

Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors

Shafaati

Jamalidoust

Kargar

et al. 2021

Microbiology and Immunology

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“…miR-199a is significantly downregulated in the tissues and sera of patients with HCC. miR-199a may be used as a potential circulating biomarker for HCC (49,50). In the present study, downregulated miR-199a-5p elevated the expression of its targets CDK4 and IGF2.…”

Section: Discussionsupporting

confidence: 52%

Identification of miRNA and mRNA expression profiles by PCR microarray in hepatitis B virus‑associated hepatocellular carcinoma

2018

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The present study aimed to identify differentially expressed microRNAs (miRNAs) and mRNAs in hepatitis B virus-associated hepatocellular carcinoma (HCC). A total of five HCC tissues and paired adjacent non-tumor tissues were screened to identify the differentially expressed miRNAs and target mRNAs using polymerase chain reaction microarrays. The interaction between differential miRNA and mRNA expression was concurrently analyzed using bioinformatics methods. A total of 32 differentially expressed miRNAs (four upregulated miRNAs and 28 downregulated miRNAs) and 16 differentially expressed mRNAs (11 upregulated mRNAs and five downregulated mRNAs) were identified. Among these, upregulated hsa-miRNA (miR)-96-5p and hsa-miR-18b-5p suppressed their target mRNAs forkhead box O1 and MET transcriptional regulator MACC1 (MACC1). Downregulation of hsa-miR-199a-5p led to upregulation of its target mRNAs, cyclin dependent kinase 4 and insulin like growth factor 2 (IGF2). The high-level expression of IGF2 mRNA and cyclin E1 mRNA was due to the low-level expression of hsa-miR-145-5p, hsa-miR-181a-5p, hsa-miR-199a-5p and hsa-miR-223a-3p, and hsa-miR-26a-5p and hsa-miR-26b-5p, respectively. The low-level expression of coronin 1A mRNA and MACC1 mRNA was due to overexpression of hsa-miR-517a-3p and hsa-miR-18a-5p, and hsa-miR-18b-5p, respectively. Numerous gene ontology terms were associated with oncogenesis. The most enriched pathways targeted by the dysregulated miRNAs and mRNAs were associated with cancer and oncogenesis pathways. The present data suggested that differential miRNA and mRNA expression is present in HCC. Thus, interactions between certain miRNAs and mRNAs may be involved in the pathogenesis of HCC.

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“…Hsa-miR-21-5p is associated with tumors in several organs [ 25 ] and several liver diseases including nonalcoholic steatohepatitis [ 26 ], drug-induced liver injury [ 27 ], and hepatocellular carcinoma [ 28 , 29 ]. However, the relationship between hsa-miR-21-5p and autoimmune disease has not been elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

et al. 2017

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Recently, there is ample evidence suggesting the important role of microRNAs (miRNAs) in autoimmune diseases via modulating B cells function. Primary biliary cholangitis (PBC) is a progressive immune-mediated liver disease with unclear pathogenic mechanism. Whether the miRNA in peripheral B cells of PBC involve the mechanisms of pathology and progression is not known. The present study explores miRNA deregulation in peripheral B-cell of PBC from stage I to IV and healthy controls. Peripheral B cells were obtained from 72 PBC patients (stage I, n = 17; stage II, n = 23; stage III, n = 16; stage IV, n = 16) and 15 healthy controls. Initially, in a discovery study, miRNA array analysis was performed, subsequently, in a validation study, quantitative PCR was used to investigate miRNA expression profile in B cells of PBS patients compared to healthy controls. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA–gene network. The discovery study identified 558 miRNAs differentially expressed in B cells of PBC patients compared to controls. Interestingly, among all differentially expressed miRNAs, hsa-miR-223-3p and hsa-miR-21-5p were the only miRNAs that showed consistent and significant down-regulation from stage I to stage III of PBC. Bioinformatics showed that potential target genes of both miRNAs involved in migration, cell differentiation, apoptosis, and signal transduction pathways. In conclusion, our results suggest that the expression profiles of miRNA in peripheral B cells of PBC patients are closely associated with the disease progression, especially the down-regulation of hsa-miR-223-3p and hsa-miR-21-5p. Taken together, our study offers novel perspectives on the role of miRNAs in PBC pathogenesis.

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Relation between microRNAs and Apoptosis in Hepatocellular Carcinoma

Cited by 17 publications

References 27 publications

Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors

Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors

Identification of miRNA and mRNA expression profiles by PCR microarray in hepatitis B virus‑associated hepatocellular carcinoma

MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

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