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

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• 作者：Kripa Patel ; Anita Kollory ; Asami Takashima ; Sibaji Sarkar ; Douglas V. Faller ; Sajal K. Ghosh ; ^{sajal@bu.edu" class="auth_mail}
• 关键词：Pancreatic cancer ; STAT3 ; Let-7 ; SOCS3 ; EMT
• 刊名：Cancer Letters
• 出版年：28 May, 2014
• 年：2014
• 卷：347
• 期：1
• 页码：54-64
• 全文大小：2686 K

文摘

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.