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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: However, the mechanisms of resistance remain unclear.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.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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MiRNA profile associated with drug resistance in pancreatic cancer cells(A) The heat map shows 33 miRNAs whose expression is altered > 4- or < 0.25-fold in gemcitabine-resistant SW1990 cells (SW1990/GEM cells) compared with SW1990 cells. (B) Validation of miR-497 expression levels by qRT-PCR. U6 served as an internal control (*P < 0.05).
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Figure 1: MiRNA profile associated with drug resistance in pancreatic cancer cells(A) The heat map shows 33 miRNAs whose expression is altered > 4- or < 0.25-fold in gemcitabine-resistant SW1990 cells (SW1990/GEM cells) compared with SW1990 cells. (B) Validation of miR-497 expression levels by qRT-PCR. U6 served as an internal control (*P < 0.05).

Mentions: To identify miRNAs associated with drug resistance in pancreatic cancer, we screened the miRNA expression profile in parental SW1990 and gemcitabine-resistant SW1990 (SW1990/GEM) cells using Illumina miRNA arrays. The criteria for identification of miRNAs associated with drug resistance were fold change > 4 or < 0.25 and P < 0.05 (Student t tests). A total of 33 miRNAs out of 1146 miRNAs probes in the Illumina microarray platform were identified, including 13 downregulated miRNAs and 20 upregulated miRNAs (Figure 1A). Among these miRNAs, miR-497 was chosen for further investigation based on the following reasons. First, miR-497 showed the largest change in expression level in SW1990/GEM cells (0.00794-fold change). Quantitative reverse-transcription polymerase chain reaction (RT-PCR) further showed that the expression level of miR-497 in SW1990/GEM cells was significantly downregulated (Figure 1B). Second, miR-497 was previously reported to be involved in regulating chemosensitivity in colorectal cancer [8].


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)

MiRNA profile associated with drug resistance in pancreatic cancer cells(A) The heat map shows 33 miRNAs whose expression is altered > 4- or < 0.25-fold in gemcitabine-resistant SW1990 cells (SW1990/GEM cells) compared with SW1990 cells. (B) Validation of miR-497 expression levels by qRT-PCR. U6 served as an internal control (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: MiRNA profile associated with drug resistance in pancreatic cancer cells(A) The heat map shows 33 miRNAs whose expression is altered > 4- or < 0.25-fold in gemcitabine-resistant SW1990 cells (SW1990/GEM cells) compared with SW1990 cells. (B) Validation of miR-497 expression levels by qRT-PCR. U6 served as an internal control (*P < 0.05).
Mentions: To identify miRNAs associated with drug resistance in pancreatic cancer, we screened the miRNA expression profile in parental SW1990 and gemcitabine-resistant SW1990 (SW1990/GEM) cells using Illumina miRNA arrays. The criteria for identification of miRNAs associated with drug resistance were fold change > 4 or < 0.25 and P < 0.05 (Student t tests). A total of 33 miRNAs out of 1146 miRNAs probes in the Illumina microarray platform were identified, including 13 downregulated miRNAs and 20 upregulated miRNAs (Figure 1A). Among these miRNAs, miR-497 was chosen for further investigation based on the following reasons. First, miR-497 showed the largest change in expression level in SW1990/GEM cells (0.00794-fold change). Quantitative reverse-transcription polymerase chain reaction (RT-PCR) further showed that the expression level of miR-497 in SW1990/GEM cells was significantly downregulated (Figure 1B). Second, miR-497 was previously reported to be involved in regulating chemosensitivity in colorectal cancer [8].

Bottom Line: However, the mechanisms of resistance remain unclear.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.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