Differential Distribution of miR-20a and miR-20b may Underly Metastatic Heterogeneity of Breast Cancers

Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecularbasis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels,with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover themechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucialmicroRNA in tumors from centers to edges.
Methods: Breast tissues from 48 patients (32 patients with breastcancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group(LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first sixspecimens were detected by microRNA array, and the second ten specimens were detected by real-time qRTPCRand Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins.
Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in theLIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than innormal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levelswere higher in both groups than in the normal group; there was no difference in mRNA levels between the edgeand center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG,and protein levels in both groups were higher than in the normal group; there was a significant difference inprotein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs(miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha).
Conclusions:Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-Aand HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven andopposing distributions to the miRNAs. It appears that one of the most important facets underlying metastaticheterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.