Altered microRNA expression profile in hepatitis B virus-related hepatocellular carcinoma

Park, Keon Uk; Seo, Young-Su; Lee, Yun‐Han; Park, Jung–Wook; Hwang, Ilseon; Kang, Koo Jeong; Nam, Jehyun; Kim, Sang Woo; Kim, Jin Young

doi:10.1016/j.gene.2015.07.053

Cited by 9 publications

(8 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taking into account the role in cancer [36,37,38,39,40,41,42,43,44,45,46] of the miRNAs identified in the discovery phase, we further investigated the expression by RT-qPCR of the 13 miRNA candidates in a cohort of 60 matched samples, (30 HCC+ vs. 30 HCC−) obtained at T0 and T1. The time difference of the mean obtained from repeated measures of the selected miRNAs in HCC+ vs HCC− patients, confirmed by bootstrap cross validation analysis on 1000 samples, evidenced the significant changes in miR-3197 and miR-1228-3p when analyzing the raw Cq expression.…”

Section: Discussionmentioning

confidence: 99%

Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals

Pascut

Cavalletto

Pratama

et al. 2019

Cancers

View full text Add to dashboard Cite

Direct antiviral agents (DAAs) have excellent efficacy against chronic hepatitis C virus (HCV) infection. Despite this strength, recent studies raised concerns about an unexpected hepatocellular carcinoma (HCC) occurrence rate after DAA therapy. In this exploratory case-control study, we evaluated the potential use of miRNAs as serum biomarkers for the detection of early HCC in DAA-treated patients. In the discovery phase, the circulating miRNome was assessed in 10 matched patients with (HCC+) or without HCC (HCC−) occurrence. Microarray analysis was performed before (T0) and after one month of the DAA therapy (T1). MiRNAs discriminating HCC+ and HCC− patients were validated in 60 samples by means of RT-qPCR. We estimated the time-averaged difference of a given miRNA between HCC+ and HCC− patients using a bootstrapped random-effect generalized least square regression model (RE-GLS). At T0, miR-1207-5p, miR-1275, miR-3197, miR-4443, miR-3178, miR-483-5p, miR-4706, miR-4793-3p and miR-1246 discriminated HCC+ from HCC− patients (p < 0.05). At T1, only miR-1180-3p, miR-1228-3p, miR-4329 and miR-4484 (p < 0.05) discriminated HCC+ from HCC− patients. The subsequent validation phase identified miR-3197 as changing with both disease and time. Our results suggest that patients might be already committed to HCC occurrence before DAA therapy. MiR-3197 shows some potential for the identification of patients at risk of HCC during DAA treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals

Pascut

Cavalletto

Pratama

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Recently, high-throughput array analyses have clearly demonstrated that miR-4417 is upregulated in many human cancers, such as breast cancer, prostate cancer, and gastrointestinal cancer [13–16]. Keon Uk Park et al reported that miR-4417 was upregulated in HCC tissues compared with non-cancerous liver tissue samples by using a microarray-based genome-wide miRNA analysis [11]. Here, we further examined the expression of miR-4417 in HCC cell lines, and confirmed that endogenous miR-4417 in HCC cell lines is indeed upregulated compared with the normal liver cell line HL-7702.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, miR-21 enhances cell proliferation, invasion, and metastasis in HCC cells and xenograft tumor growth in mouse models, providing a candidate target for cancer gene therapy [10]. miR-4417 is a newly discovered miRNA that was reported to be upregulated in HCC tissues compared with adjacent normal tissues [11]. It was also reported that the top 5 putative targets of miR-4417 were SOS1 , FAF2 , PAXIP1 , C1orf95 , and WDR48 [11].…”

Section: Introductionmentioning

confidence: 99%

“…miR-4417 is a newly discovered miRNA that was reported to be upregulated in HCC tissues compared with adjacent normal tissues [11]. It was also reported that the top 5 putative targets of miR-4417 were SOS1 , FAF2 , PAXIP1 , C1orf95 , and WDR48 [11]. However, the direct functional targets and biological roles of miR-4417 in HCC cells remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miR-4417 Targets Tripartite Motif-Containing 35 (TRIM35) and Regulates Pyruvate Kinase Muscle 2 (PKM2) Phosphorylation to Promote Proliferation and Suppress Apoptosis in Hepatocellular Carcinoma Cells

et al. 2017

View full text Add to dashboard Cite

BackgroundMicroRNAs (miRNAs) are a class of small non-coding RNAs that are strongly involved in various types of carcinogenesis, including hepatocellular carcinoma (HCC). This study aimed to clarify whether miR-4417 promotes HCC growth by targeting TRIM35 and regulating PKM2 phosphorylation.Material/MethodsOnline software, including TargetScan and miRanda, was used to predict the potential target of miR-4417. Real-Time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of mRNA and protein, respectively. Cell proliferation was measured by MTT assay and apoptosis in A549 cells was examined by flow cytometry.ResultsBioinformatics reveal that TRIM35 mRNA contains 1 conserved target site of miR-4417. High level of miR-4417 and low levels of TRIM35 mRNA and protein were observed in HCC cells compared with a normal liver cell line. Biological function analysis showed that miR-4417 inhibitor inhibits cell proliferation and promotes apoptosis in HCC cells. Furthermore, we verified that TRIM35 is a functional target of miR-4417 by use of luciferase reporter assay, and TRIM35 overexpressing showed an elevation of proliferation and a reduction of apoptosis in HCC cells. We subsequently investigated whether miR-4417 and TRIM35 regulate HCC cell proliferation and apoptosis through PKM2 Y105 phosphorylation, and the results supported our speculation that miR-4417 targets TRIM35 and regulates the Y105 phosphorylation of PKM2 to promote hepatocarcinogenesis.ConclusionsOur findings indicate that miR-4417 may function as an oncogene in HCC and is a potential alternative therapeutic target for this deadly disease.

show abstract

“…About 600,000 patients die every year due to HCC . The current available modalities to treat HCC include surgical removal of effected areas followed by radiotherapy or chemotherapy with 18% five‐year survival rate which shows the limited efficacy of cancer modalities against HCC . Currently, sorafenib is the only Food and Drug Administration approved drug for treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Deoxyelephantopin induces apoptosis in HepG2 cells via oxidative stress, NF‐κB inhibition and mitochondrial dysfunction

Mehmood

Maryam

et al. 2016

BioFactors

View full text Add to dashboard Cite

Deoxyelephantopin (DET), a naturally occurring sesquiterpene lactone present in Chinese medicinal herb, Elephantopus scaber has been shown to exert anti-inflammatory as well as anticancer effects in various cancer cells of human origin in vitro. However, the exact molecular mechanism underlying DET-induced apoptosis remains largely unexplored, particularly in human hepatocellular carcinoma G2 (HepG2) cells. In the present study, we found that DET inhibits proliferation and induces apoptosis in HepG2 cells in a dose-dependent manner. This DET-mediated apoptosis was found to be associated with reactive oxygen species generation, glutathione depletion and decreased activity of thioredoxin reductase, mitochondrial membrane potential disruption, Bcl-2 family proteins modulation, cytochrome c release, caspases-3 activation, PARP cleavage and inhibition of NF-jB activation. DET inhibited the constitutive as well as induced-translocation of NF-jB into nucleus and augmented the apoptotic effect of Gemcitabine. IKK-16 (NF-jB inhibitor) further enhanced the cytotoxicity of DET and gemcitabine indicating that DET induces apoptosis in HepG2 cells at least partially through inhibition of NF-jB activation. Further mechanistic study demonstrated that DET inhibits the translocation of constitutive as well as induced-NFjB into nucleus by decreasing phosphorylation of IrBa. Moreover, pretreatment of cells with 3 mM NAC reversed DETmediated cell death and NF-jB inhibition, indicating that DET exerts its anticancer effects mainly through oxidative stress. Therefore, DET may be developed into a lead chemotherapeutic drug as a single agent or in combination with clinical drugs for the effective treatment of liver cancer.

show abstract

Altered microRNA expression profile in hepatitis B virus-related hepatocellular carcinoma

Cited by 9 publications

References 41 publications

Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals

Serum miRNA Are Promising Biomarkers for the Detection of Early Hepatocellular Carcinoma after Treatment with Direct-Acting Antivirals

miR-4417 Targets Tripartite Motif-Containing 35 (TRIM35) and Regulates Pyruvate Kinase Muscle 2 (PKM2) Phosphorylation to Promote Proliferation and Suppress Apoptosis in Hepatocellular Carcinoma Cells

Deoxyelephantopin induces apoptosis in HepG2 cells via oxidative stress, NF‐κB inhibition and mitochondrial dysfunction

Contact Info

Product

Resources

About