microRNA-21 Regulates Stemness in Pancreatic Ductal Adenocarcinoma Cells

• Published in: International journal of molecular sciences 2022-01, Vol.23 (3), p.1275
• Main Authors: Mortoglou, Maria, Miralles, Francesc, Arisan, Elif Damla, Dart, Alwyn, Jurcevic, Stipo, Lange, Sigrun, Uysal-Onganer, Pinar
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aldehyde dehydrogenase; Aldehydes; Antigens; Biological activity; Cancer; cancer stem cells; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; CD44 antigen; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chemokine receptors; Chemoresistance; CRISPR; CXCR4 protein; Epithelial-Mesenchymal Transition; Gene expression; Gene Expression - genetics; Gene Expression Regulation, Neoplastic - genetics; Humans; Hyaluronan Receptors - metabolism; Medical prognosis; Mesenchyme; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - physiology; non-coding RNAs; Pancreatic cancer; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Receptors, CXCR4 - metabolism; Stem cells; Transcriptome - genetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031275

Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer (PCa) with a low survival rate. microRNAs (miRs) are endogenous, non-coding RNAs that moderate numerous biological processes. miRs have been associated with the chemoresistance and metastasis of PDAC and the presence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs). In this study, we investigated the role of miR-21, which is highly expressed in Panc-1 and MiaPaCa-2 PDAC cells in association with CSCs. Following miR-21 knockouts (KO) from both MiaPaCa-2 and Panc-1 cell lines, reversed expressions of epithelial-mesenchymal transition (EMT) and CSCs markers were observed. The expression patterns of key CSC markers, including CD44, CD133, CX-C chemokine receptor type 4 (CXCR4), and aldehyde dehydrogenase-1 (ALDH1), were changed depending on miR-21 status. miR-21 (KO) suppressed cellular invasion of Panc-1 and MiaPaCa-2 cells, as well as the cellular proliferation of MiaPaCa-2 cells. Our data suggest that miR-21 is involved in the stemness of PDAC cells, may play roles in mesenchymal transition, and that miR-21 poses as a novel, functional biomarker for PDAC aggressiveness.