MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9

• Published in: Aging (Albany, NY.) Vol. 13; no. 14; pp. 18924 - 18945
• Main Authors: Xue, Yuzheng, Wu, Tielong, Sheng, Yingyue, Zhong, Yao, Hu, Benshun, Bao, Chuanqing
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 31.07.2021
• Subjects: 3' Untranslated Regions; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis - genetics; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Proto-Oncogene Proteins c-myb - metabolism; Research Paper; Xenograft Model Antitumor Assays; NEDD9; pancreatic cancer; epithelial-mesenchymal transition; miR-1252-5p; Myb
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.203344

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. We studied the gain and loss of function of miR-1252-5p in the PAC cell lines and . The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay. Expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples, and its expression is negatively associated with adverse clinical features and poor prognosis. and experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of PAC cells, and miR-1252-5p knockdown enhances these biological behaviors. MiR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'- untranslated region. Further mechanism research revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of PAC's biological behaviors. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter. MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.