MicroRNA let-7 downregulates STAT3 phosphorylation in pancreatic cancer cells by increasing SOCS3 expression.
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.
Cancer Center, Boston University School of Medicine, Boston, MA, United States.
Kripa
K
Patel
Cancer Center, Boston University School of Medicine, Boston, MA, United States.
Anita
A
Kollory
Cancer Center, Boston University School of Medicine, Boston, MA, United States.
Asami
A
Takashima
Cancer Center, Boston University School of Medicine, Boston, MA, United States.
Sibaji
S
Sarkar
Cancer Center, Boston University School of Medicine, Boston, MA, United States.
Douglas V
DV
Faller
Cancer Center, Boston University School of Medicine, Boston, MA, United States. Electronic address: sajal@bu.edu.
Sajal K
SK
Ghosh
D001483:Base Sequence; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
D017931:DNA Primers; D035683:MicroRNAs; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C487931:mirnlet7 microRNA, human
EMT; Let-7; Pancreatic cancer; SOCS3; STAT3