Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients

Mourad, Lobna; El‐Ahwany, Eman; Zoheiry, Mona; Abu-Taleb, Hoda; Hassan, Marwa; Ouf, Amged; Rahim, Ali Abdel; Hassanien, Moataz; Zada, Suher

doi:10.1080/15384047.2018.1423922

Cited by 28 publications

(18 citation statements)

References 30 publications

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“…In addition, the correlation between miR-139 or KPNA2 expression and HBV or HCV remain largely unknown. Mourad et al has reported that circulating miR-139 level was down-regulated in HCV-induced HCC, but they did not investigate the role of miR-139 in this type of HCC [43]. In the future study, we will investigate the roles of miR-139 and KPNA2 in HCC formation and development under the background of HBV or HCV infection.…”

Section: Discussionmentioning

confidence: 95%

MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2

Zhang

Wang

Liang

et al. 2019

J Exp Clin Cancer Res

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Background MicroRNA-139-5p (miR-139) has been shown to play important roles in hepatocellular carcinoma (HCC) development. However, the exact mechanism of miR-139 in HCC remains largely unknown. Methods We investigated the function in human cell lines and patient tissue samples by experimental techniques in molecular biology including Co-IP assay, cell viability assay, quantitative real-time-PCR, et al. In addition, datasets were used to verify the results by database analysis. Statistical analysis was performed by using the GraphPad Prism 6 (GraphPad Software Inc., USA). A P value < 0.05 was defined as statistically significant. Results In this study, we found that miR-139 was significantly down-regulated in HCC. MiR-139 level was negatively associated with the stage of HCC, and HCC patients with higher miR-139 level had longer overall survival (OS) than these having lower miR-139 expression. Overexpression of miR-139 led to reduced cell viability, elevated apoptosis, and decreased colony forming, migratory and invasive capacities in HCC cells, while down-regulation of miR-139 led to opposite phenotypes. MiR-139 also inhibited HCC growth in a xenograft mouse model. We identified karyopherin alpha 2 (KPNA2) as a direct target of miR-139. KPNA2 is up-regulated in HCC and higher KPNA2 level is associated with poor patient prognosis. Silencing of KPNA2 expression led to similar phenotypic changes as miR-139 overexpression. Restoration of KPNA2 attenuated the suppressive effects of miR-139 overexpression on cell viability, apoptosis, colony formation, migration and invasion. In addition, miR-139 overexpression and KPNA2 depletion led to decreased nucleus level of POU class 5 homeobox 1 (POU5F1) and c-myc, two well-known pro-oncogenes. Conclusion In together, these data revealed the essential roles of the miR-139/KPNA2 axis in HCC.

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Section: Discussionmentioning

confidence: 95%

MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2

Zhang

Wang

Liang

et al. 2019

J Exp Clin Cancer Res

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“…Thus, Li et al showed that microRNA-139 was reduced in serum of HCC patients as compared with chronic hepatitis B (HBV) control patients, with an AUC of 0.761, specificity of 58.1%, and sensitivity of 80.6% (Table 4) [52]. In another recent study, serum levels of microRNA-139 were very low in HCC patients compared with both chronic hepatitis C patients (HCV) and liver cirrhosis patients, suggesting that microRNA-139 could be an early marker in detection of HCC-induced HCV [53].…”

Section: Resultsmentioning

confidence: 99%

DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is a frequently encountered cancer type, and its alarming incidence is explained by genetic and epigenetic alterations. Epigenetic changes may represent diagnostic and prognostic biomarkers of HCC. In this review we discussed deoxyribonucleic acid (DNA) hypomethylation, DNA hypermethylation, and aberrant expression of small non-coding ribonucleic acid (RNA), which could be useful new biomarkers in the early diagnosis of HCC. We selected the articles on human subjects published in English over the past two years involving diagnostic markers detected in body fluids, cancer diagnosis made on histopathological exam, and a control group of those with benign liver disease or without liver disease. These biomarkers need further investigation in clinical trials to develop clinical applications for early diagnosis and management of HCC.

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“…miR-16-1 is a regulator of gene expression at the post-transcriptional level. Studies have reported that miRNAs are often increased in certain cancer types, including breast cancer ( 13 ), hepatocellular carcinoma ( 14 ) and CC ( 9 , 15 – 20 ). miR-15a and miR-16-1 form part of a cluster in an intron region of the deleted in lymphocytic leukemia 2 (DLEU2) transcript on chromosome 13q14.3, which is frequently deleted in chronic lymphocytic leukemia.…”

Section: Introductionmentioning

confidence: 99%

An increase of microRNA‑16‑1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR‑HPV in liquid cytology samples

et al. 2020

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Studies of cervical cancer (CC) have reported that microRNA-16-1 (miR-16-1), which is an oncomiR, is increased in the tissues and cell lines of CC. The aim of the present study was to investigate the association of miRNA-16-1 expression level with squamous cell carcinoma (SCC), the presence of squamous intraepithelial lesions (SIL) and the integration of high-risk human papillomavirus (HR-HPV) DNA. The current study analyzed 80 samples obtained from women by liquid-based cytology, which revealed that 20 were negative for SIL (NSIL) and without HPV, 20 were low-grade SIL (LSIL), 20 were high-grade SIL (HSIL), and 20 were diagnosed as SCC with HR-HPV. The genotyping of the viral DNA was conducted via an INNO-LiPA-HPV array, the expression of miR-16-1 was determined by reverse transcription-quantitative PCR, and the physical state of the HR-HPV was ascertained by in situ hybridization with amplification with tyramide. A total of eight HR-HPV genotypes were distinguished; the most frequent of these being HPV16, followed by multiple infection with HR-HPV (including HPV16). The mixed state of the HR-HPV was observed in 60 and 65% of LSIL and HSIL cases, respectively, while an integrated HR-HPV state was identified in 90% of cases with SCC. The expression level of miR-16-1 increased according to the grade of SIL, and cases with HSIL exhibited a significantly higher miR-16-1 expression level compared with women with NSIL (P<0.001; Table II). It can therefore be determined that the expression of miR-16-1 effects cellular proliferation, due to the viral integration of various HR-HPV genotypes in unique infection or in multiple infection. Thus, the overexpression of miR-16-1 could be monitored in women with LSIL, in order to discard a major lesion.

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Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients

Cited by 28 publications

References 30 publications

MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2

MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2

DNA Methylation and Micro-RNAs: The Most Recent and Relevant Biomarkers in the Early Diagnosis of Hepatocellular Carcinoma

An increase of microRNA‑16‑1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR‑HPV in liquid cytology samples

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