Prognostic value of microRNAs in hepatocellular carcinoma: a meta-analysis

Abstract

BackgroundNumerous articles reported that dysregulated expression levels of miRNAs correlated with survival time of HCC patients. However, there has not been a comprehensive meta-analysis to evaluate the accurate prognostic value of miRNAs in HCC.DesignMeta-analysis.Materials and MethodsStudies, published in English, estimating expression levels of miRNAs with any survival curves in HCC were identified up until 15 April, 2017 by performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two independent authors. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS).Results54 relevant articles about 16 miRNAs, with 6464 patients, were ultimately included. HCC patients with high expression of tissue miR-9 (HR = 2.35, 95% CI = 1.46–3.76), miR-21 (HR = 1.76, 95% CI = 1.29–2.41), miR-34c (HR = 1.64, 95% CI = 1.05–2.57), miR-155 (HR = 2.84, 95% CI = 1.46–5.51), miR-221 (HR = 1.76, 95% CI = 1.02–3.04) or low expression of tissue miR-22 (HR = 2.29, 95% CI = 1.63–3.21), miR-29c (HR = 1.35, 95% CI = 1.10–1.65), miR-34a (HR = 1.84, 95% CI = 1.30–2.59), miR-199a (HR = 2.78, 95% CI = 1.89–4.08), miR-200a (HR = 2.64, 95% CI = 1.86–3.77), miR-203 (HR = 2.20, 95% CI = 1.61–3.00) have significantly poor OS (P < 0.05). Likewise, HCC patients with high expression of blood miR-21 (HR = 1.73, 95% CI = 1.07–2.80), miR-192 (HR = 2.42, 95% CI = 1.15–5.10), miR-224 (HR = 1.56, 95% CI = 1.14–2.12) or low expression of blood miR-148a (HR = 2.26, 95% CI = 1.11–4.59) have significantly short OS (P < 0.05).ConclusionsIn conclusion, tissue miR-9, miR-21, miR-22, miR-29c, miR-34a, miR-34c, miR-155, miR-199a, miR-200a, miR-203, miR-221 and blood miR-21, miR-148a, miR-192, miR-224 demonstrate significantly prognostic value. Among them, tissue miR-9, miR-22, miR-155, miR-199a, miR-200a, miR-203 and blood miR-148a, miR-192 are potential prognostic candidates for predicting OS in HCC.

XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging miR-155-5p

“…These results are consistent with previous reports. 7 28 35 36 By dual luciferase reporter assay and examining XIST expression status in XIST overexpressing HepG2 cells transfected with miR-155-5p mimic, we identified XIST as a direct target of miR-155-5p, and overexpressing XIST was able to partially rescue the protein expression levels of some HCC suppressing genes previously identified as direct targets of miR-155-5p in miR-155-5p mimic-transfected HepG2 cells, including PTEN and SOX6. 16 18 37 The HCC suppressing role of XIST antagonizing that of miR-155-5p was further revealed by cell functional assays: XIST overexpression not only decreased cell proliferation while increasing apoptosis, but also increased the susceptibility of HepG2 cells to cisplatin treatment, which was undermined by miR-155-5p mimic transfection.…”

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation

“…Their results suggest that circulating miR-221 expression could be a prognostic marker. In a large screening study, Zhang et al [97] investigated the potential prognostic miRNAs using data from 54 relevant articles and 6464 patients and identified circulating miR-148a and miR-192 as reliable prognostic markers in HCC. Jin et al [87] also revealed that six miRNAs (miR-424-5p, miR-101-3p, miR-128, miR-139-5p, miR-382-5p, and miR-410) were significantly related with overall survival rate in 116 HCC patients and had potential to be good biomarkers for predicting prognosis.…”

Prospects of Noncoding RNAs in Hepatocellular Carcinoma

“…It is clear that miRNA plays a role in proliferation, persistence, invasion, metastasis, and prognostic indicators of hepatocellular carcinoma [ 36 – 39 ]. In liver cancer tissue, there are many abnormally expressed miRNAs, such as miR-224, miR-221, and miR-21 that influence hepatocellular carcinoma [ 40 – 42 ]. miR-224 has been shown to target HOXD10 RNA and enhance both PAK4-mediated phosphorylation and MMP-9 to promote the invasion and metastasis of cancer cells [ 43 ].…”