Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R

Autor: Joseph A. Fontana, Farhan Murshed, Jayanta Kumar Das, Arun K. Rishi, Marcia I. Dawson, Lulu Farhana
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Microarrays
Cancer Treatment
Gene Expression
lcsh:Medicine
Adamantane
Apoptosis
Receptor
IGF Type 1
Molecular Cell Biology
Gene expression
Tumor Cells
Cultured
Signaling in Cellular Processes
Promoter Regions
Genetic
lcsh:Science
Apoptotic Signaling
Inhibitor of apoptosis domain
Gene knockdown
Multidisciplinary
Gene Expression Regulation
Neoplastic
Hyaluronan Receptors
Oncology
Gene Knockdown Techniques
Neoplastic Stem Cells
Medicine
Research Article
Signal Transduction
Protein Binding
Biology
Pancreatic Cancer
Proto-Oncogene Proteins c-myb
Downregulation and upregulation
Cell Line
Tumor
Spheroids
Cellular
Pancreatic cancer
miR-150
Gastrointestinal Tumors
microRNA
Genetics
medicine
Humans
lcsh:R
Computational Biology
Cancers and Neoplasms
CD24 Antigen
medicine.disease
Genes
bcl-2
Pancreatic Neoplasms
MicroRNAs
Cinnamates
Cancer research
lcsh:Q
Zdroj: PLoS ONE, Vol 8, Iss 5, p e61015 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: MicroRNAs have been implicated in many critical cellular processes including apoptosis. We have previously found that apoptosis in pancreatic cancer cells was induced by adamantyl retinoid-related (ARR) molecule 3-Cl-AHPC. Here we report that 3-Cl-AHPC-dependent apoptosis involves regulating a number of microRNAs including miR-150* and miR-630. 3-Cl-AHPC stimulated miR-150* expression and caused decreased expression of c-Myb and IGF-1R in the pancreatic cancer cells. 3-Cl-AHPC-mediated reduction of c-Myb resulted in diminished binding of c-Myb with IGF-1R and Bcl-2 promoters, thereby causing repression of their transcription and protein expression. Over-expression of miR-150* also resulted in diminished levels of c-Myb and Bcl-2 proteins. Furthermore, the addition of the miRNA inhibitor 2'-O-methylated miR-150 blocked 3-Cl-AHPC-mediated increase in miR-150* levels and abrogated loss of c-Myb protein. Knockdown of c-Myb in PANC-1 cells resulted in enhanced apoptosis both in the presence or absence of 3-Cl-AHPC confirming the anti-apoptotic property of c-Myb. Overexpression of miR-630 also induced apoptosis in the pancreatic cancer cells and inhibited target protein IGF-1R mRNA and protein expression. Together these results implicate key roles for miR-150* and miR-630 and their targeting of IGF-1R to promote apoptosis in pancreatic cancer cells.
Databáze: OpenAIRE
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