Abstract
Purpose: This study tried to explore whether members of miR-92a family contribute to early diagnosis and prognosis for human cancers and how they work.Methods: Integrated meta-analysis retrieved from public repositories was employed to assess the clinical roles of the miR-92a family for cancer diagnosis and prognosis. Expression level of miR-92a was detected by the TCGA database and was confirmed by non-small-cell lung cancer (NSCLC) tissues. Targets of miR-92a were predicted using starbase, and validated by dual luciferase assay. Correlation between miR-92a and the target gene was assessed by linkedOmics while expression of the target gene and its role in cancer prognosis were analyzed with UALCAN and Gepia.Results: We recognized the miR-92a family could serve as a potential diagnostic biomarker with a pooled sensitivity of 0.85 [0.81–0.88] and specificity of 0.86 [0.83–0.90]. The overall hazard ratio (HR) was 2.26 [95% CI: 1.70–3.00] for high expression groups compared to low expression groups. Expression of miR-92a was identified to be upregulated in NSCLC, especially in lung squamous cell carcinoma (LUSC). Results from starbase and dual luciferase assay indicated the regulator of G-protein signaling 3 (RGS3) was a direct target of miR-92a. Statistical negative correlation was found for the expression of miR-92a and RGS3. In addition, expression of RGS3 was downregulated in NSCLC and patients with the high expression had a poor prognosis (HR = 1.3) for LUSC patients. However, results were to the contrary for lung adenocarcinoma (HR = 0.7).Conclusion: This study revealed that miR-92a family could be ideal biomarkers for cancer diagnosis and prognosis, which might function through targeting RGS3.
Highlights
MicroRNAs are small, conserved, single-stranded, non-coding RNAs, which adjust gene expression in the post-transcriptional level (Lagos-Quintana et al, 2001)
Demographic information and data for meta-analysis including sensitivity (SEN), specificity (SPE), true positive (TP), false positive (FP), false negative (FN), true negative (TN), hazard ratio (HR) with 95% 95% confidence interval (CI) was collected from included literature by two authors (MJ and XY-L) independently
Results indicated that the expression of miR-92a was low in Non-small-cell lung cancer (NSCLC) compared with normal tissues (P = 0.005 for lung adenocarcinoma (LUAD), Figure 6A; P < 0.001 for lung squamous cell carcinoma (LUSC), Figure 6B)
Summary
MicroRNAs (miRNAs) are small, conserved, single-stranded, non-coding RNAs, which adjust gene expression in the post-transcriptional level (Lagos-Quintana et al, 2001). MiRNAs participate in a series of processes including cellular proliferation, differentiation, and apoptosis and promote tumorigenesis and metastasis (Nana-Sinkam and Croce, 2011; Bracken et al, 2016). Role of miR-92a Family on Cancer (C13orf25) gene. Both miR-363 and miR-92a-2 whose primiRNAs have been proven to be Kis ncRNAs are encoded in the miR-106-363 cluster from q26.2 of X chromosome. The abnormal expression of miR-92a members has been found in different malignant human tumors (Hu et al, 2012; Zhu et al, 2014; Fan et al, 2016; Motawi et al, 2016; Elhamamsy et al, 2017; Fujiwara et al, 2017; Ding et al, 2018)
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