Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses

Abstract

MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR-132-3p and CCA remains unknown. In the present study, the clinical role of miR-132-3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription-quantitative PCR (RT-qPCR), CCA-associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA-microarray or miRNA-sequencing data were screened, and meta-analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR-132-3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA-sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein-protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non-tumor biliary epithelium. The meta-analyses comprised 10 groups of RT-qPCR data, eight GEO microarray datasets and one TCGA miRNA-sequencing dataset. The SMD of miR-132-3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR-132-3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR-132-3p in the early stage of CCA (stages I–II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III–IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR-132-3p level in low-grade CCA (grades G1-G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high-grade CCA (grades G3-G4) (P=0.037). Furthermore, 555 potential target genes of miR-132-3p in CCA were mainly enriched in the ‘Focal Adhesion-PI3K-Akt-mTOR-signaling pathway’. In conclusion, upregulation of miR-132-3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.

Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation

“…In pancreatic cancer (PC), miR-132-3p was demonstrated to be significantly up-regulated compared with the normal and benign tissues, which contribute to the malignant progression of PC via regulating caspases-7 23 . Besides, overexpression of miR-132-3p has also been reported in cholangiocarcinoma and glioma endothelial tissues 24 , 25 . On the contrary, in colorectal and breast cancers 26 , 27 , miR-132-3p expression has been shown to be down-regulated and to play an anti-tumorigenic role in the progression of those cancers.…”

Immunohistochemical basigin expression level in thyroid cancer tissues

“…This study included The Gene Expression Database (GEO) [ 24 ], ArrayExpress [ 25 ], Oncomine [ 26 ], and The Sequence Read Archive (SRA) [ 27 ] in order to search both Chinese and English medical literature for microarray data of BSG to analyze its clinical value in TC. Our search included data entered into the databases from the beginning to February 21, 2020.…”

Immunohistochemical Basigin Expression Level in Thyroid Cancer Tissues

“…This study included The Gene Expression Database (GEO) [24], ArrayExpress [25], Oncomine [26], and the The Sequence Read Archive (SRA) [27] in order to search both Chinese and English medical literature for microarray data of BSG to analyze its clinical value in TC. Our search included data entered into the databases from the beginning to February 21, 2020.…”