Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis

Abstract

Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.

Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments

“…ITGA2 has been reported to play a critical role in modulating the pancreatic cancer immune response by transcriptionally increasing the expression of PD-L1 in cancer cells (Ren et al, 2019). At the same time, it has been reported that ITGA2 is associated with unfavorable survival of PDAC patients by affecting the malignant biological behavior of pancreatic cancer cells (Rozengurt, Sinnett-Smith & Eibl, 2018;Shimomura et al, 2020;Yan et al, 2020). Considering that the mechanism of ITGA2 in PDAC has been studied partly, we focused on FN1 which has no mechanism study in PDAC for further study.…”

RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p

“…Our recent studies show that some passenger miRNAs have a tumor suppressor function in cancer cells. (e.g., miR-148-5p, miR-145-3p, miR-143-5p, miR-30c-2-3p, and miR-30a-3p) [19,26,41,42]. Those miRNA duplexes and their target oncogenic genes are closely associated with cancer pathogenesis [19,26,41,42].…”

“…(e.g., miR-148-5p, miR-145-3p, miR-143-5p, miR-30c-2-3p, and miR-30a-3p) [19,26,41,42]. Those miRNA duplexes and their target oncogenic genes are closely associated with cancer pathogenesis [19,26,41,42].…”

A Potential circRNA-miRNA-mRNA Regulatory Network in Asthmatic Airway Epithelial Cells Identified by Integrated Analysis of Microarray Datasets

“…However, hsa-miR-30d-3p has not been reported in asthma yet. Hsa-miR-30a-3p was reported to regulate the tumorigenesis in various cancer, such as gastric cancer (Wang et al, 2019b), lung adenocarcinoma (Wang et al, 2020), and pancreatic ductal adenocarcinoma (Shimomura et al, 2020). Li and others reported that hsa-miR-30a-3p regulates eosinophil activity through targeting CCR3 in asthma (Li et al, 2020).…”