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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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Related in: MedlinePlus

Expression levels and prognostic values of miR-497 in pancreatic cancer tissues(A) The expression levels of miR-497 in a panel of 90 pancreatic cancer and tumor-adjacent tissues were detected by ISH (200×). (B) The expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues were analyzed using Pearson χ2 test. (C) Kaplan-Meier survival analysis in pancreatic cancer patients based on miR-497 expression in primary tumors.
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Figure 7: Expression levels and prognostic values of miR-497 in pancreatic cancer tissues(A) The expression levels of miR-497 in a panel of 90 pancreatic cancer and tumor-adjacent tissues were detected by ISH (200×). (B) The expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues were analyzed using Pearson χ2 test. (C) Kaplan-Meier survival analysis in pancreatic cancer patients based on miR-497 expression in primary tumors.

Mentions: We next evaluated the expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues by in situ hybridization (ISH). ISH staining revealed that miR-497 was located in the cytoplasm (Figure 7A). Tissue samples were scored for high and low miR-497 expression, as described in Materials and Methods. Among the 90 pancreatic cancer samples, 69 showed low expression of miR-497 and 21 showed high expression. In comparison, among the matched tumor-adjacent tissues, only eight showed low expression of miR-497, whereas 82 showed high expression. The expression of miR-497 in pancreatic cancer tissues was significantly decreased compared with that in tumor-adjacent tissues (P=0.000) (Figure 7B).


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)

Expression levels and prognostic values of miR-497 in pancreatic cancer tissues(A) The expression levels of miR-497 in a panel of 90 pancreatic cancer and tumor-adjacent tissues were detected by ISH (200×). (B) The expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues were analyzed using Pearson χ2 test. (C) Kaplan-Meier survival analysis in pancreatic cancer patients based on miR-497 expression in primary tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Expression levels and prognostic values of miR-497 in pancreatic cancer tissues(A) The expression levels of miR-497 in a panel of 90 pancreatic cancer and tumor-adjacent tissues were detected by ISH (200×). (B) The expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues were analyzed using Pearson χ2 test. (C) Kaplan-Meier survival analysis in pancreatic cancer patients based on miR-497 expression in primary tumors.
Mentions: We next evaluated the expression levels of miR-497 in 90 pancreatic cancer tissue samples and matched tumor-adjacent tissues by in situ hybridization (ISH). ISH staining revealed that miR-497 was located in the cytoplasm (Figure 7A). Tissue samples were scored for high and low miR-497 expression, as described in Materials and Methods. Among the 90 pancreatic cancer samples, 69 showed low expression of miR-497 and 21 showed high expression. In comparison, among the matched tumor-adjacent tissues, only eight showed low expression of miR-497, whereas 82 showed high expression. The expression of miR-497 in pancreatic cancer tissues was significantly decreased compared with that in tumor-adjacent tissues (P=0.000) (Figure 7B).

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