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

• 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
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2014.01.020

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.