Increased expression of MUSASHI1 in epithelial breast cancer cells is due to down regulation of miR-125b

Abstract

Background Musashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression of MSI1 has a role in solid tumor progression. There are different factors that regulate MSI1 expression in various cancer tissues including microRNAs which are considered as one of the most important of these factors. The aim of our study is identification of the molecular cause of maximal expression of MSI1 in epithelial breast cancer cell lines. Results Among predicted microRNAs, miR-125b, miR-637 and miR-802 were able to significantly reduce the luciferase activity. In addition, the relative expression of these three miRNAs were measured in the cancerous cell lines that results showed a significant reduction in expression of all microRNAs. On the other hand, only the overexpression of miR-125b caused a change in the expression pattern of MSI1 in breast epithelial cancer cell lines. Accordingly, our results demonstrated that the exogenous expression of miR-125b decreased not only the MSI1 protein but also expression of epithelial markers in breast cancer cells. Conclusions The results of luciferase reporter assay showed that MSI1 is a direct target for miR-125b in epithelial breast cancer cells. Moreover, higher amount of MSI1 in those cell lines seems due to the reduced amount of miR-125b, which is responsible for epithelial features of those kinds of cancer cells. Therefore, the modulation of miR-125b may be a potential approach to help to combat against epithelial breast tumors.

The Musashi RNA-binding proteins in female cancers: insights on molecular mechanisms and therapeutic relevance

“…MSI-1 was co-localized with E-cadherin, a key epithelial marker, in immunohistochemistry measurements. Finally, MSI-1 and MSI-2 were higher expressed in predominantly luminal breast cancer cell lines compared to basal cells, a finding reproduced by another group [ 65 ]. Katz et al also found that MSI-1 overexpression decreased migration and MSI-2 overexpression reduced ductal branching [ 60 ].…”

“…Using methylation analyses in primary breast cancer specimens, Kagara and colleagues found that MSI-1 promotor methylation (which was inversely correlated with gene expression) was lowest in TNBC, similar to other stem cell markers, including CD44 and CD133 [ 62 – 64 ]. Finally, Forouzanfar and colleagues demonstrated that MSI-1 expression depends on miR-125b in breast cancer [ 65 ].…”

Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis

“…Among them, the expression level of miR-637 in various cancer tissues was significantly lower than that in adjacent tissues, including glioblastoma and lowgrade gliomas (GBM/LGG) [8][9][10][11], papillary thyroid carcinoma (PTC) [12,13], non-small cell lung cancer (NSCLC) [14], gastric cancer (GC) [15][16][17], hepatocellular carcinoma (HCC) [18][19][20][21], CRC [22], pancreatic ductal adenocarcinoma (PDAC) [23], human cholangiocarcinoma (CHOL) [24], oral squamous cell carcinoma (OSCC) [25], prostate cancer (PCa) [26], ovarian cancer (OC) [27,28], triple-negative breast cancer (TNBC) [29], cervical cancer (CCa) [30], osteosarcoma (SaOS) [31,32], multiple myeloma (MM) [33], chronic myeloid leukemia (CML) [34]. In addition, the expression level of miR-637 was lower in the cell lines of various cancer cells than the corresponding normal cell lines, including PTC [12,13], GC [17], HCC [18,21], OSCC [35], PDAC [23], CHOL [36], TNBC [37], breast cancer (BRCA) [38], SaOS [31], etc. In the serum of CHOL patients, the expression level of miR-637 was lower than that of healthy people [39].…”