ALCAM is indirectly modulated by miR-125b in MCF7 cells

Abstract

MicroRNA (miRNA) deregulation is associated with various cancers. Among an expanding list of cancer-related miRNAs, deregulation of miR-125b has been well documented in many cancers including breast. Based on current knowledge, miR-125b is considered to be a tumor suppressor in breast cancers. While important messenger RNA (mRNA) targets have been defined for miR-125b, here, we aimed to further investigate direct/indirect consequences of miR-125b expression in breast cancer cells by using a transcriptome approach. Upon miR-125b expression, a total of 138 cancer-related genes were found to be differentially expressed in breast cancer cells. While only a few of these were predicted to be direct mRNA targets, majority of the gene expression changes were potentially downstream and indirect effects of miR-125b expression. Among these, activated leukocyte antigen molecule (ALCAM) mRNA and protein levels were found to be highly significantly increased upon miR-125b expression. Given the tumor suppressor role of miR-125b in our model system, upon silencing of ALCAM expression, cell proliferation rate re-increased in miR-125b-expressing cells. While ALCAM's possible context-dependent roles are not clear in breast cancer, a diverse expression pattern of ALCAM mRNA was detected in a panel of breast cancer patient samples. Differentially expressed/regulated cancer-related genes upon miR-125b expression along with the significant increase of ALCAM are of future interest to understand how deregulated expression of miR-125b may have a tumor suppressor role in breast and other cancers.

Key Factors in Breast Cancer Dissemination and Establishment at the Bone: Past, Present and Future Perspectives

“…ALCAM was found to be one of a panel of genes whose expression was altered following expression of miR-125b. Expression of miR-125b enhanced both ALCAM mRNA and protein levels, which was found to influence MCF-7 growth using a further shRNA study [122]. It has also recently been reported that inhibition of miR-214, overexpression of miR-148b or a combination can inhibit tumour cell crossing of the vessel endothelium through a negative regulation of ALCAM and integrin α5 [123].…”

miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

“…MicroRNAs (miRNAs, miRs) are a class of small non-coding RNA that regulates gene expression by targeting the 3' untranslated region (UTR) of targeted mRNAs (7)(8)(9). Previous studies indicated that the abnormal expression of miRNA was involved in tumorigenesis with a tissue-specific expression pattern (6,7,10).…”