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 AMPKα1 might be the direct target gene of miR-148b, and overexpressed AMPKα1 inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKα1 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 AMPKα1. Our present results implicate the potential effects of miR-148b on prognosis and treatment of pancreatic cancer.
Highlights
MiRNAs are a class of small noncoding RNAs, which contain of about 22 nucleotides. miRNAs bind to partially complementary sequences in the 30-untranslated region (UTR) of specific target mRNA, resulting in either mRNA degradation or translation inhibition [1]
The results showed that deregulated expression of miR-148b significantly correlated with increased tumor size, late tumor–node–metastasis (TNM) stage, lymphatic invasion, and distant metastasis
Similar results were obtained in BXPC-3 cells. These results indicate that miR-148b regulates apoptosis, cell-cycle arrest, and invasion by the direct target of AMPactivated protein kinase a1 (AMPKa1)
Summary
MiRNAs are a class of small noncoding RNAs, which contain of about 22 nucleotides. miRNAs bind to partially complementary sequences in the 30-untranslated region (UTR) of specific target mRNA, resulting in either mRNA degradation or translation inhibition [1]. MiRNAs are a class of small noncoding RNAs, which contain of about 22 nucleotides. MiRNAs bind to partially complementary sequences in the 30-untranslated region (UTR) of specific target mRNA, resulting in either mRNA degradation or translation inhibition [1]. Growing evidence suggests that miRNAs play an important role in various biologic processes, including cell proliferation, development, and differentiation [2, 3]. Increasing numbers of miRNAs have been observed in various types of cancer and may be involved in modulating cancer cell behaviors [4,5,6,7].
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