Abstract
Background/aimsStudies have shown that miR-146a-5p was differentially expressed in diverse cancers, but the associations between miR-146a-5p expression and prognosis across multiple types of cancer as well its potential targets and downstream pathways have not been comprehensively analyzed. In this study, we performed the first meta-analysis of the prognostic value of miR-146a-5p expression in diverse malignancies and explored prospective targets of miR-146a-5p and related signaling pathways.MethodsA thorough search for articles related to miR-146a-5p was performed, and RNA-seq data from The Cancer Genome Atlas (TCGA) and microarray data from gene expression omnibus profiles were used to collect information about the prognostic value of miR-146a-5p. A comprehensive meta-analysis was conducted. Twelve platforms in miRWalk 2.0 were applied to predict targets of miR-146a-5p. TCGA RNA-seq data were used to validate the inverse relationships between miR-146a-5p and its likely targets. Subsequently, gene ontology and pathway analyses were conducted using Funrich version 3.1.3. Potential protein–protein interaction (PPI) networks were constructed. Potential target genes of miR-146a-5p in lung cancer were validated by RT-qPCR.ResultsWe included 10 articles in the meta-analysis. In a pooled analysis, the high miR-146a-5p expression group showed a better overall survival in solid cancers, particularly in reproductive system cancers and digestive system cancers. A total of 120 predicted target genes were included in a bioinformatics analysis. Five pathways involving phospholipase C (PLC) and aquaporins (AQPs) were the most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, the PPI network displayed the related signaling pathways and interactions among proteins. AQP1 and FYN were validated by RT-qPCR to be potential targets of miR-146a-5p in lung cancer.ConclusionThere is a close link between high miR-146a-5p expression and better overall survival in 21 types of solid cancer, especially in reproductive system and digestive system cancers. Furthermore, miR-146a-5p could inhibit diverse malignancies by modulating pathways linked to PLC or AQPs. In summary, miR-146a-5p is a potential prognostic biomarker and therapeutic target for various cancers.
Highlights
Cancer is a serious threat to human health, with almost 1,735,350 newly diagnosed cancer cases and nearly 609,640 cancer-related deaths in the United States in 2018 [1, 2]
Validation of potential targets of miR‐146a‐5p through RT‐qPCR Previously, we found that miR-146a-5p showed a decreased expression in lung cancer tissues compared to normal lung tissues [25]
Using an integrated meta-analysis, we found that lower miR-146a-5p expression was correlated with worse outcomes in solid cancers, especially in reproductive system cancers and digestive system cancers
Summary
Cancer is a serious threat to human health, with almost 1,735,350 newly diagnosed cancer cases and nearly 609,640 cancer-related deaths in the United States in 2018 [1, 2]. Multiple factors regulate tumorigenesis and tumor development by altering DNA replication, transcription, and translation. The discovery of these factors, including microRNAs (miRNAs) and long non-coding RNAs, was considered a breakthrough for the early diagnosis and prevention of cancers. MiRNAs are single-stranded non-coding RNAs (18–22 nucleotides) with vital roles in the regulation of biological processes, including transcription, translation, cell cycle, and organismal development [5]. These molecules are linked to post-transcriptional regulation by interacting with corresponding messenger RNAs (mRNAs). MiRNAs are promising therapeutic candidates for metastatic cancer [5]
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