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RNA-binding protein Musashi2 regulates Hippo signaling via SAV1 and MOB1 in pancreatic cancer
- Source :
- Medical oncology (Northwood, London, England). 37(9)
- Publication Year :
- 2020
-
Abstract
- Musashi 2 (MSI2), a member of the Musashi RNA-binding family, is reported to be an oncoprotein in pancreatic ductal adenocarcinoma (PDAC), but the mechanisms of MSI2 in the development and progression of PDAC have not been fully demonstrated. In this research, we studied the clinical significance, biologic effects and the underlying mechanism of MSI2 in the progression of PDAC. The expression of MSI2, Mps-binding protein 1 (MOB1) and Salvador family WW domain-containing protein 1 (SAV1) in PDAC tissues were analyzed immunohistochemically. The biologic effects of MSI2 regarding PDAC cell proliferation, migration and invasion were studied using gain- and loss-of-function assays. MSI2 regulated Hippo signaling pathway via SAV1 and MOB1 was tested in several PDAC cell lines, and the mechanisms were studied using molecular biologic methods. The expression of MSI2 was significantly increased in PDAC cell lines and tissues, and positively associated with tumor poorer differentiation, lymph nodes metastasis and TNM stages. Overexpression of MSI2 promoted PDAC cells proliferation, migration and invasion. Further studies demonstrated that MSI2 regulated the Hippo signaling pathway via directly binding to the mRNAs of SAV1 and MOB1, and controlled the translation and stability of SAV1 and the translation of MOB1. This study demonstrated that MSI2 regulated the Hippo signaling pathway via suppressing SAV1 and MOB1 at post-transcriptional level and promoted PDAC progression.
- Subjects :
- Cancer Research
endocrine system diseases
RNA-binding protein
Cell Cycle Proteins
Biology
Protein Serine-Threonine Kinases
Metastasis
03 medical and health sciences
0302 clinical medicine
Pancreatic cancer
Cell Line, Tumor
medicine
Biomarkers, Tumor
Humans
Hippo Signaling Pathway
Cell Proliferation
Musashi2
Hippo signaling pathway
Cell growth
RNA-Binding Proteins
Translation (biology)
Hematology
General Medicine
medicine.disease
Prognosis
digestive system diseases
Chemokine CXCL10
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms
Oncology
Hippo signaling
030220 oncology & carcinogenesis
Cancer research
Signal Transduction
Subjects
Details
- ISSN :
- 1559131X
- Volume :
- 37
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Medical oncology (Northwood, London, England)
- Accession number :
- edsair.doi.dedup.....b185b469ebcb7ea43016a1d6f02dc64b