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MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis.

Xu J, Wang T, Cao Z, Huang H, Li J, Liu W, Liu S, You L, Zhou L, Zhang T, Zhao Y - Oncotarget (2014)

Bottom Line: Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities.Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets.Overexpression of miR-497 inhibited tumor growth in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. These authors contributed equally to this work.

ABSTRACT
Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159-6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.

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MiR-497 suppressed tumor growth in vivoMice were transplanted with SW1990 cells stably overexpressing miR-497 or control cells, and tumor growth was monitored. Tumor growth in vivo was analyzed by analysis of variance. Upper panel: tumors from experimental and control mice. Lower panel: tumor growth curves showing miR-497 inhibition of tumor growth.
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Figure 5: MiR-497 suppressed tumor growth in vivoMice were transplanted with SW1990 cells stably overexpressing miR-497 or control cells, and tumor growth was monitored. Tumor growth in vivo was analyzed by analysis of variance. Upper panel: tumors from experimental and control mice. Lower panel: tumor growth curves showing miR-497 inhibition of tumor growth.

Mentions: We next established an in vivo model to determine the role of miR-497 on tumor growth in mice. SW1990 cells stably overexpressing miR-497 or control cells were transplanted into mice, and tumor growth was monitored. Tumor size in mice transplanted with SW1990 cells stably overexpressing miR-497 was significantly smaller than those from control mice (P=0.000) (Figure 5).


MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis.

Xu J, Wang T, Cao Z, Huang H, Li J, Liu W, Liu S, You L, Zhou L, Zhang T, Zhao Y - Oncotarget (2014)

MiR-497 suppressed tumor growth in vivoMice were transplanted with SW1990 cells stably overexpressing miR-497 or control cells, and tumor growth was monitored. Tumor growth in vivo was analyzed by analysis of variance. Upper panel: tumors from experimental and control mice. Lower panel: tumor growth curves showing miR-497 inhibition of tumor growth.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196178&req=5

Figure 5: MiR-497 suppressed tumor growth in vivoMice were transplanted with SW1990 cells stably overexpressing miR-497 or control cells, and tumor growth was monitored. Tumor growth in vivo was analyzed by analysis of variance. Upper panel: tumors from experimental and control mice. Lower panel: tumor growth curves showing miR-497 inhibition of tumor growth.
Mentions: We next established an in vivo model to determine the role of miR-497 on tumor growth in mice. SW1990 cells stably overexpressing miR-497 or control cells were transplanted into mice, and tumor growth was monitored. Tumor size in mice transplanted with SW1990 cells stably overexpressing miR-497 was significantly smaller than those from control mice (P=0.000) (Figure 5).

Bottom Line: Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities.Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets.Overexpression of miR-497 inhibited tumor growth in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. These authors contributed equally to this work.

ABSTRACT
Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159-6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.

Show MeSH
Related in: MedlinePlus