Authors: Zhao G; Zhang JG; Liu Y; Qin Q; Wang B; Tian K; Liu L; Li X; Niu Y; Deng SC; Wang CY
Abstract: miRNAs are small noncoding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-148b has been found in some types of cancer, but its expression and potential biologic role in pancreatic cancer are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 48 pairs of human pancreatic cancer tissues and five cell lines. Furthermore, the deregulated miR-148b was correlated with increased tumor size, late tumor-node-metastasis stage, lymphatic invasion, distant metastasis, and worse prognosis in pancreatic cancer. Functional studies indicated overexpression of miR-148b dramatically suppressed the growth of cancer cells, attributable to induction of apoptosis and cell-cycle arrest at S-phase. Meanwhile, miR-148b remarkably inhibited invasion and enhanced chemosensitivity of pancreatic cancer cells. Moreover, ectopic expression of miR-148b was able to inhibit tumorigenicity in nude mice. Further studies revealed that AMPKalpha1 might be the direct target gene of miR-148b, and overexpressed AMPKalpha1 inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKalpha1 with RNA interference inhibited the growth of pancreatic cancer cells in vitro and in vivo and also induced apoptosis, cell-cycle arrest, and inhibited invasion of cancer cells, which is consistent with the effects of miR-148b overexpression. In conclusion, miR-148b can inhibit cell proliferation, invasion, and enhance chemosensitivity of pancreatic cancer by targeting AMPKalpha1. Our present results implicate the potential effects of miR-148b on prognosis and treatment of pancreatic cancer.
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Journal: Molecular cancer therapeutics Volume: 12 Issue: 1 Pages: 83-93 Date: Nov. 23, 2012 PMID: 23171948 |
Zhao G, Zhang JG, Liu Y, Qin Q, Wang B, Tian K, Liu L, Li X, Niu Y, Deng SC, Wang CY (2013) miR-148b functions as a tumor suppressor in pancreatic cancer by targeting AMPKα1. Molecular cancer therapeutics 12: 83-93.
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