MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection

Zhang, Erlei; Gu, Jin; Zhang, Zunyi; Dong, Kai; Liang, Benjia; Huang, Zhiyong

doi:10.3892/ol.2017.6178

Cited by 4 publications

(4 citation statements)

References 50 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides miR-138-5p, 4 miRNAs (miR-135a-1, miR-let-7 g, miR-1226, miR-564) out of total 16 miRNAs at this locus have been reported to perform tumor suppressive functions in various cancers 127 – 131 . Furthermore, upregulation of six miRNAs has been identified in different cancer types, including miR-4271 132 , miR-191 133 – 135 , miR-425 136 – 138 , miR-4793 139 , miR-2115 140 , and miR-4443 141 , suggesting potential oncogenic functions in these cancers.…”

Section: Discussionmentioning

confidence: 99%

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Chhabra

Rockfield

Guergues

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Malignant transformation of fallopian tube secretory epithelial cells (FTSECs) is a key contributing event to the development of high-grade serous ovarian carcinoma (HGSOC). Our recent findings implicate oncogenic transformative events in chronic iron-exposed FTSECs, including increased expression of oncogenic mediators, increased telomerase transcripts, and increased growth/migratory potential. Herein, we extend these studies by implementing an integrated transcriptomic and mass spectrometry-based proteomics approach to identify global miRNA and protein alterations, for which we also investigate a subset of these targets to iron-induced functional alterations. Proteomic analysis identified > 4500 proteins, of which 243 targets were differentially expressed. Sixty-five differentially expressed miRNAs were identified, of which 35 were associated with the “top” proteomic molecules (> fourfold change) identified by Ingenuity Pathway Analysis. Twenty of these 35 miRNAs are at the 14q32 locus (encoding a cluster of 54 miRNAs) with potential to be regulated by DNA methylation and histone deacetylation. At 14q32, miR-432-5p and miR-127-3p were ~ 100-fold downregulated whereas miR-138-5p was 16-fold downregulated at 3p21 in chronic iron-exposed FTSECs. Combinatorial treatment with methyltransferase and deacetylation inhibitors reversed expression of these miRNAs, suggesting chronic iron exposure alters miRNA expression via epigenetic alterations. In addition, PAX8, an important target in HGSOC and a potential miRNA target (from IPA) was epigenetically deregulated in iron-exposed FTSECs. However, both PAX8 and ALDH1A2 (another IPA-predicted target) were experimentally identified to be independently regulated by these miRNAs although TERT RNA was partially regulated by miR-138-5p. Interestingly, overexpression of miR-432-5p diminished cell numbers induced by long-term iron exposure in FTSECs. Collectively, our global profiling approaches uncovered patterns of miRNA and proteomic alterations that may be regulated by genome-wide epigenetic alterations and contribute to functional alterations induced by chronic iron exposure in FTSECs. This study may provide a platform to identify future biomarkers for early ovarian cancer detection and new targets for therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Chhabra

Rockfield

Guergues

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…For example, levels of miR-21 in serum exosomes are significantly higher in patients with HCC compared to controls [6, 7]. In whole serum, several studies have identified potential diagnostic miRNAs [8–14]; however, no consensus has been reached on a panel of miRNAs that robustly identifies HCC at an early stage of the disease. In tissue, several miRNAs are found to be dysregulated between tumor and normal tissue [15–19], for instance miR-21, miR-199, and miR-221.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

et al. 2019

View full text Add to dashboard Cite

BackgroundThe expression of microRNAs (miRNAs) is a promising prognostic and diagnostic tool in hepatocellular carcinoma (HCC). Here we performed small RNA sequencing (sRNA-seq) of tissue, serum and serum exosomes to investigate changes in miRNA expression between the different sample types and correlated the expression with clinical parameters. We also performed gene expression arrays on tumor and normal tissue.ResultsPaired tissue, serum and serum exosomes sequencing revealed consistent positive correlation of miR-21 between serum exosomes and tumor tissue, indicating that miR-21 could be exported from tissue to circulation via exosomes. We found that let-7 miRNAs are generally upregulated in serum exosomes compared to whole serum, indicating that these miRNAs could be preferentially loaded into exosomes. Comparing serum from HCC patients with serum from healthy individuals revealed a global increase of miRNAs in serum from HCC patients, including an almost 4-fold increase of several miRNAs, including the liver-specific miR-122. When correlating miRNA expression with clinical parameters we detected significant association between hepatitis B virus (HBV) infection and miR-122 in serum as well as several serum and tissue-miRNAs that correlated with surgery type. We found that miR-141 and miR-146 correlated with cirrhosis in tumor tissue and normal tissue, respectively. Finally, high expression of miR-21 in tumors were associated with poor survival. Focusing on gene expression we found several significant messenger RNAs (mRNAs) between tumor and normal tissue and a Gene Ontology (GO) analysis revealed that these changes were mainly related to cell cycle and metabolism. Further, we detected mRNAs that correlated with cirrhosis and HBV infection in tissue. Finally, GO analysis of predicted targets for miRNAs down-regulated in tumor found that these were enriched for functions related to collagen synthesis.ConclusionsOur combined data point to altered miRNA and mRNA expression contributing to both generally impaired lipid metabolism and increased cell proliferation and a miRNA-driven increase in collagen synthesis in HCC. Our results further indicate a correlation in miRNA expression between exosomes, serum, and tissue samples suggesting export from tumors via exosomes. This correlation could provide a basis for a more tumor-specific miRNA profile in serum.

show abstract

“…Zhang et al7 reported in their study that a panel of 3 miRNAs when combined with AFP had a higher diagnostic efficacy in the diagnosis of HCC than AFP alone. The current study revealed a significant difference in miR-215 expression levels among the three studied main groups.…”

Section: Discussionmentioning

confidence: 99%

“…Mature miRNAs may interact with the 3′-untranslated regions (UTRs) of target mRNAs to form RNA-induced silencing complexes, resulting in inhibition of translation or mRNA cleavage 6. As well, previous studies have revealed that miRNAs may regulate gene expression at posttranscriptional level and perform a role in regulating epigenetic machinery, including DNA methylation and histone modification 7…”

Section: Introductionmentioning

confidence: 99%

<p>Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma</p>

Ali¹,

Higazi²,

Moness³

et al. 2019

CEG

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It has been widely established that the early detection of HCC enables more treatment options with improvements in prognosis and survival.ObjectivesThe aim of this study was to assess the diagnostic accuracy of both circulating miR-215 and squamous cell carcinoma antigen-IgM (SCCA-IgM) as serum biomarkers for HCC by examining their diagnostic sensitivity, specificity, accuracy, and predictive values in hepatitis C virus (HCV)-induced HCC patients.Subjects and methodsThis study included 60 patients with HCV-related HCC. In addition, 60 patients with HCV-related liver cirrhosis (LC) and 60 apparently healthy subjects were involved, and served as diseased and healthy control groups, respectively. The relative expression levels of miR-215 were detected using quantitative real-time PCR. SCCA-IgM levels in serum were measured by enzyme immunoassay. We used receiver operating characteristic (ROC) curve to calculate the diagnostic accuracy against alpha-fetoprotein (AFP).ResultsRelative miR-215 expression levels increased the most in HCC patients compared to that in healthy or diseased controls (P<0.001). Serum concentration of SCCA-IgM was significantly higher in HCC group than that in the two control groups. We performed multivariate analysis using AFP level, focal lesion size, and portal vein thrombosis as independent variables. ROC curves showed that the optimum diagnostic miR-215 cutoff value for identifying HCC patients from cirrhotic ones was 417 (sensitivity, 97%; specificity, 91%) and for SCCA-IgM was 95 AU/mL (sensitivity, 92%; specificity, 98%). Moreover, the superiority of both miR-215 and SCCA-IgM to AFP is obvious in our study and this superiority is more evident in distinguishing HCC with AFP levels <200 ng/mL and HCC patients with small-sized focal lesions from cirrhotic patients.ConclusionCell-free miR-215 and serum SCCA-IgM could be used for early diagnosis of HCC either each one as a single marker or with AFP complement measurement.

show abstract

MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection

Cited by 4 publications

References 50 publications

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Global miRNA/proteomic analyses identify miRNAs at 14q32 and 3p21, which contribute to features of chronic iron-exposed fallopian tube epithelial cells

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

<p>Clinical significances and diagnostic utilities of both miR-215 and squamous cell carcinoma antigen-IgM versus alpha-fetoprotein in Egyptian patients with hepatitis C virus-induced hepatocellular carcinoma</p>

Contact Info

Product

Resources

About