MicroRNA let-7 downregulates STAT3 phosphorylation in pancreatic cancer cells by increasing SOCS3 expression

Abstract Although dispensable for normal pancreatic function, STAT3 signaling is frequently activated in pancreatic cancers. Consistent downregulation of expression of microRNA let-7 is also characteristic of pancreatic ductal adenocarcinoma (PDAC) biopsy specimens. We demonstrate in this study that...

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Bibliographic Details
Published in:Cancer letters 2014-05, Vol.347 (1), p.54-64
Main Authors: Patel, Kripa, Kollory, Anita, Takashima, Asami, Sarkar, Sibaji, Faller, Douglas V, Ghosh, Sajal K
Format: Article
Language:English
Subjects:
Base Sequence
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Cell cycle
Cell growth
Cell Line
Cell Line, Tumor
DNA Primers
Down-Regulation - physiology
EMT
Hematology, Oncology and Palliative Medicine
Humans
Kinases
Let-7
Medical research
MicroRNAs - physiology
Microscopy, Fluorescence
Mutation
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Phosphorylation
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
SOCS3
STAT3
STAT3 Transcription Factor - metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins - metabolism
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Summary:Abstract Although dispensable for normal pancreatic function, STAT3 signaling is frequently activated in pancreatic cancers. Consistent downregulation of expression of microRNA let-7 is also characteristic of pancreatic ductal adenocarcinoma (PDAC) biopsy specimens. We demonstrate in this study that re-expression of let-7 in poorly-differentiated PDAC cell lines reduced phosphorylation/activation of STAT3 and its downstream signaling events and reduced the growth and migration of PDAC cells. Let-7 re-expression did not repress expression of STAT3 protein or its activator cytokine interleukin 6 (IL-6). However, let-7 re-expression enhanced cytoplasmic expression of suppressor of cytokine signaling 3 (SOCS3), which blocks STAT3 activation by JAK2. Our study thus identified a mechanism by which STAT3 signaling can be inhibited in pancreatic cancer cells by modifying let-7 expression.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2014.01.020