Circulating microRNA-145 as a diagnostic biomarker for non-small-cell lung cancer: A systemic review and meta-analysis

Abstract

Background: MicroRNAs (miRNAs), a class of small non-coding, highly stable RNAs, have been reported to have diagnostic value for variety types of cancers. Objectives: To assess the diagnostic value of circulating miR-145 for non-small cell lung cancer (NSCLC) by using systemic review and meta-analysis. Methods: A systematic literature search was conducted in five databases until 20 February 2020 to identify diagnostic trials of miR-145 in the diagnosis of NSCLC. The quality of included studies was assessed by the QUADAS-2 tool with Review Manager 5.3, and the summary receiver operating characteristic (SROC) curve was plotted by STATA 13.1 software. Results: A total of 1394 patients from 11 data sets in trials (published in nine studies) were recruited. The area under the curve of the SROC was 0.83. According to the meta regression, the specimen selection was considered the source of heterogeneity, the SROC in serum (0.90 (95% CI 0.87, 0.92), the sensitivity was 0.84 (95% CI 0.79, 0.89), and the specificity was 0.80 (95% CI 0.71, 0.89)) was obviously higher than that in plasma (SROC=0.75). Conclusion: Serum miR-145 might be served as a potentially useful biomarker for NSCLC diagnosis. However, due to the existing limited-quality research, more large-scale and multicenter studies are required for further verification.

Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands

“…These findings shed light on the function of miR-133a and the molecular mechanisms underlying miR-133a-mediated EGFR/AKT/ERK signaling pathway downregulation in NSCLC [64][65][66]. Further, miR-145 significantly suppressed EGFR expression and inhibited cancer cell growth compared with negative control miRNA in A549 NSCLC cells [7,83,84]. Transfection with miR-146a mimic in NSCLC cells resulted in the downregulation of EGFR mRNA.…”

“…The correlation between EGFR activation and miR-145 expression in normal human lung epithelia cell line (BEAS-2B), LADC cell lines with wild-type EGFR (A549 and H292), and with mutant EGFR (H1975 and H1650) was investigated, where miR-145 levels were found to be strongly correlated with p-EGFR. EGF suppressed the expression of miR-145, particularly in BEAS-2B and A549 cells [7, 83,84,123]. After inhibiting p-EGFR with AG1478, miR-145 was up-regulated, and treatment with AG1478 increased miR-145 by 67.5% in H1975 cells.…”

“…After inhibiting p-EGFR with AG1478, miR-145 was up-regulated, and treatment with AG1478 increased miR-145 by 67.5% in H1975 cells. Further, p-EGFR activated the ERK1/2 signaling pathway, and U0126 (ERK1/2 inhibitor) reversed the downregulation of miR-145 caused by EGFR activation [7, 83,84]. Likewise, miR-134 suppressed EGFR-associated signaling by down-regulating p-EGFR in A549, H520 H1299, and H1975 cells.…”

“…Although various mechanisms that drive resistance to EGFR-inhibitors have been identified, many cases have unclear mechanisms. Many research studies pointed out the implication of numerous miRNAs in modulating NSCLC sensitivity to erlotinib [20,[57][58][59][60]83,84,169,186]. An exciting study by Gober et al predicted a 13-miRNA signature for the response to the EGFR-TKI erlotinib in NSCLC cell lines and tumors and discriminated primarily from metastatic tumors [72,185,186,189].…”

“…miR-145 could induce apoptosis and increase erlotinib levels in A549 NSCLC cells. The pretreatment with miR-145 reduced tumor growth by suppressing the expression of EGFR induced cell arrest of the G1/S cycle phase, and improved the sensitivity of A549, NSCLC cell line, to erlotinib [7, 83,84].…”