A Novel miRNA–mRNA Axis Involves in Regulating Transcriptional Disorders in Pancreatic Adenocarcinoma

Abstract

Background Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA–mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored. Methods We compared differentially expressed miRNAs (DEMIs) and differentially expressed genes (DEGs) in PAAD and normal tissues from the Gene Expression Omnibus (GEO) database. Transcription factors (TFs) were obtained from FunRich. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs and DEMIs were implemented using Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, key miRNAs and targeted mRNAs were identified by assessment of their expression and prognosis in UALCAN and Kaplan–Meier plotters. In the last step, the candidate miRNA–mRNA selected was confirmed by real-time quantitative polymerase chain reaction (qRT-PCR). Results We distinguished 62 significant DEMIs, 1314 upregulated DEGs, and 1110 downregulated DEGs. The top 10 TFs were identified. In total, there were 160 hub genes obtained by intersecting the set of 2224 predicted targets with the set of significant DEGs. And we selected 8 key miRNAs. Furthermore, low expression of miR-455-3p in PAAD tissue was closely connected with poor prognosis, and only 5 target mRNAs were predicted to be increased in PAAD tissue with poor prognosis. Therefore, a novel miRNA–hub gene regulatory network in PAAD was constructed. Finally, in vitro experiments indicated that miR-455-3p expression was decreased in PAAD sample. HOXC4, DLG4, DYNLL1 and FBXO45 were validated by qRT-PCR as highly probable targets of miR-455-3p. Conclusion A novel miRNA–mRNA axis has been discovered that may be involved in the regulation of transcriptional disorders and affected the survival of PAAD patients, which would provide a novel strategy for the treatment of PAAD.

Construction and validation of an aging-related gene signature predicting the prognosis of pancreatic cancer

“…The expression level of HOXC4 mRNA in tumor group was significantly higher than that in normal samples. HOXC4 is the target of miR-455-3p and its formation of miR-455-3p-HOXC4 axis may be closely related to the metastasis and prognosis of human pancreatic cancer ( Shang et al, 2021 ). GH1 participates in the formation of GIPC1, which is necessary for integrin circulation during cell migration, angiogenesis and cytokinesis.…”

Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation

“…Overexpression of FBXO45 facilitated the ubiquitination of IGF2BP1 and upregulation of PLK1, which conferred to liver tumorigenesis [30]. FBXO45 expression was high and associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC) [31,32]. Moreover, bioinformatics analysis showed that FBXO45 could be a potential oncogene in esophageal cancer [33].…”

The development of a novel signature based on the m6A RNA methylation regulator-related ceRNA network to predict prognosis and therapy response in sarcomas

“…This miRNA can impair HCC cell malignancy via suppression of insulin growth factor receptor expression, thereby disrupting glycolysis ( Hu et al, 2019 ; Jiang et al, 2019 ). Gao et al (2018) , Yang et al (2017) , and Shang et al (2021) reported that low expression of miR-455-3p in non-small-cell lung cancer, esophageal squamous cell carcinoma (ESCC), and pancreatic cancer (PAAD) tissues was strongly associated with poor prognosis. miR-455-3p acts as a tumor suppressor in esophageal squamous cell carcinoma (ESCC) and inhibits cell proliferation and invasion by targeting FAM83F.…”