microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway.

Abstract

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.

• Authors: Xiao-Li Yang, Yu-Shui Ma, Yu-Shan Liu, Xiao-Hui Jiang, Hua Ding, Yi Shi, Cheng-You Jia, Gai-Xia Lu, Dan-Dan Zhang, Hui-Min Wang, Pei-Yao Wang, Zhong-Wei Lv, Fei Yu, Ji-Bin Liu, Da Fu
• Journal: Cellular signalling (Cell Signal) Vol. 84 Pg. 110025 (08 2021) ISSN: 1873-3913 [Electronic] England
• PMID: 33915247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Blood Proteins
• MicroRNAs
• Phosphoproteins
• platelet protein P47
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Blood Proteins
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplastic Stem Cells (metabolism)
• Pancreatic Neoplasms (pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoproteins
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (genetics)