Expression of miR-9 and miR-200c, ZEB1, ZEB2 and E-cadherin in Non-Small Cell Lung Cancers in Iran

Abstract

MicroRNAs (miRNAs) exert a critical influence on physiological and pathological processes through posttranscriptional modification of their mRNA targets. They play important roles in tumorigenesis and are considered to be potential diagnostic and prognostic biomarkers with various cancers. MiR-200c and miR-9 are regulatory elements that can have dual impacts as oncogenes and/or tumor suppressor genes. MiR-200c regulates two transcription factors, ZEB1 and ZEB2, while miR-9 is a regulatory factor for the E-cadherin protein which has a critical function in cell-cell junctions and is inhibited by two transcription factors ZEB1 and ZEB2. In this study, expression levels of miR-200c and miR-9, ZEB-1, ZEB-2 and E-cadherin were assessed in 30 non-small cell lung cancers (NSCLCs) by real-time qPCR. MiR-9 was down-regulated significantly in tumor tissues compared to normal adjacent tissues, while there was no significant change in expression level of miR-200c. On the other hand, ZEB1 demonstrated significant increase and ZEB2a decrease at the mRNA level. These results indicate roles for miR-9 and ZEB1 in genesis of lung cancer, although clinico-pathological associations were not evident. Further studies are necessary to assess implications for treatment of lung cancer.

Keywords: MicroRNAs; miR-200c; miR-9; non-small cell lung cancer.

Figure 1

A: miR-9 expression level in NSCLC patients compared to normal adjacent tissue. miR-9 expression was significantly decreased in NSCLC samples compared to normal adjacent tissues (p-value <0.0001). B: Down_regulation of miR-200c was found in patients with NSCLC compared to normal adjacent tissue. (p-value=0.22)C:No significant correlation was found between the expression levels of E-cadherin in patients with NSCLC compared to adjacent normal tissue (p-value=0.82). D:ZEB1 expression level in NSCLC patients compared to normal adjacent tissue. ZEB1 expression level was significantly increased in NSCLC samples compared to normal adjacent tissue (p-value=0.0206). E: Association of ZEB2 expression level in patients with NSCLC compared to adjacent normal tissues. ZEB2 expression level was significantly decreased in NSCLC samples compared to normal adjacent tissues (P value= 0.0207)

Figure 2

A: miR-9 expression was downregulated in adenocarcinomas (Adeno) subtype compared to squamous cell subtype (SCC) patients. B: Correlation of miR-9 and E-cadherin expression level in all tumor samples (n=30).

Figure 3

A: Correlation of miR-200c and ZEB family expression level. Down_regulation of miR-200c expression leads to a decrease in ZEB1 expression level. B: Correlation of ZEB family and E-cadherin expression level (ANOVA). Up-regulation of ZEB1is associated with a significant down_regulation E-cadherin expression level (t-test) (p-value<0.05).