Abstract 859: miR-638, a novel tumor suppressor for ER-negative breast cancer.

MicroRNAs (miRNAs) are endogenous non-coding RNAs of 19∼25 nt in length, which regulate many protein-coding genes. miRNA dysregulation is observed in a variety of cancers, including breast cancer. miRNAs have emerged as an important set of biomarkers. miRNA profiling studies have led to the identification of miRNAs that are aberrantly expressed in human breast cancer, with miR-10b, miR-125b and miR-145 being down-regulated and miR-21, and 155 being up-regulated. In our previous miRNA expression profiling studies using microdissected FFPE tissues, we identified 8 clusters of miRNAs, which discrete the normal and breast lesions such as ADH, DCIS and IDC. miR-638 is one of the differentially expressed miRNAs during breast cancer progression. We first sought to determine the expression of miR-638 in different breast cancer cell lines such as MCF-7, Hs578T, T47D and MDA-MB-231 using qRT-PCR, which shows a very low expression compared to normal tissues. This led us to hypothesize that miR-638 may function as a tumor suppressor during breast cancer development. To determine the role of miR-638 in both ER+ and ER- breast cancer cells, we transfected miR-638 mimic oligos and scrambled oligo mocks into MCF-7 (ER+), T47D (ER+), MDA-MB-231 (ER-) and Hs578T (ER-) cells. After 48 hours, we found that the proliferation rate was significantly down-regulated in ER- cells but not in ER+ cells by MTT assay. Our preliminary matrigel analysis shows that miR-638 overexpressing MDA-MB-231 cells had 3∼4 fold invasiveness decrease compared to the control. Further, our TargetScan analysis revealed that BRCA1 is one of the direct targets of miR-638 among the 30 conservative target genes. We found that overexpression of miR-638 resulted in an upregulation of BRCA1 mRNA expressions in ER- cell lines, MDA-MB-231 and Hs578T but not in ER+ cell lines, T47D and MCF-7. Taken together, these findings showed that miR-638 may function as a tumor suppressor in ER- breast cancer, possibly in part by upregulating BRCA1 tumor suppressor gene. Further functional analysis is underway to decipher the exact role of miR-638 in ER- breast cancer, which could become a therapeutic target. Citation Format: Jin Peng, Yebo Fu, Rachel F. Brem, Christine B. Teal, Sidney W. Fu. miR-638, a novel tumor suppressor for ER-negative breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 859. doi:10.1158/1538-7445.AM2013-859