1. Musashi2 promotes the progression of pancreatic cancer through a novel ISYNA1-p21/ZEB-1 pathway.
- Author
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Zhou L, Sheng W, Jia C, Shi X, Cao R, Wang G, Lin Y, Zhu F, Dong Q, and Dong M
- Subjects
- Adult, Aged, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal secondary, Cell Line, Tumor, Cell Movement, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, Cyclin-Dependent Kinase Inhibitor p21 genetics, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Humans, Intramolecular Lyases antagonists & inhibitors, Intramolecular Lyases biosynthesis, Intramolecular Lyases genetics, Kaplan-Meier Estimate, Liver Neoplasms secondary, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms mortality, Prognosis, RNA Interference, RNA, Small Interfering genetics, RNA, Small Interfering pharmacology, Tumor Suppressor Protein p53 physiology, Zinc Finger E-box-Binding Homeobox 1 biosynthesis, Zinc Finger E-box-Binding Homeobox 1 genetics, Carcinoma, Pancreatic Ductal pathology, Cyclin-Dependent Kinase Inhibitor p21 physiology, Intramolecular Lyases physiology, Neoplasm Proteins physiology, Pancreatic Neoplasms pathology, RNA-Binding Proteins physiology, Signal Transduction physiology, Zinc Finger E-box-Binding Homeobox 1 physiology
- Abstract
Our previous studies found overexpression of Musashi2 (MSI2) conduced to the progression and chemoresistance of pancreatic cancer (PC) by negative regulation of Numb and wild type p53 (wtp53). Now, we further investigated the novel signalling involved with MSI2 in PC. We identified inositol-3-phosphate synthase 1 (ISYNA1) as a novel tumour suppressor regulated by MSI2. High MSI2 and low ISYNA1 expression were prevalently observed in 91 PC tissues. ISYNA1 expression was negatively correlated with MSI2 expression, T stage, vascular permeation and poor prognosis in PC patients. What's more, patients expressed high MSI2 and low ISYNA1 level had a significant worse prognosis. And in wtp53 Capan-2 and SW1990 cells, ISYNA1 was downregulated by p53 silencing. ISYNA1 silencing promoted cell proliferation and cell cycle by inhibiting p21 and enhanced cell migration and invasion by upregulating ZEB-1. However, MSI2 silencing upregulated ISYNA1 and p21 but downregulated ZEB-1, which can be rescued by ISYNA1 silencing. Moreover, reduction of cell migration and invasion resulting from MSI2 silencing was significantly reversed by ISYNA1 silencing. In summary, MSI2 facilitates the development of PC through a novel ISYNA1-p21/ZEB-1 pathway, which provides new gene target therapy for PC., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Published
- 2020
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