MiRNA and Target Oncogene Regulation in Triple Negative Breast Cancer: An Age, Ethnic and Environmental Related Neoplastic Event

Abstract

Triple-negative breast cancer is a type of aggressive breast cancer without the immunohistochemical expression of estrogen receptors, progesterone receptors and human epidermal growth factor receptor-2; with poor prognosis, greater relapse risk and worse survival in general. Its proportion in all breast cancer cases ranges from 15 to 20%. Triple negative breast cancer is more prevalent among younger women, particularly African, African-American, Latino and obese women. This observed prevalence, is an age and ethnic related factor which fingers estrogenic agents as a common feature in TNBC occurrence. Inherited variation in the let-7 binding site on the KRAS oncogene has been revealed to confer increased susceptibility to triple negative breast cancer, especially in premenopausal, African-American and Hispanic women. About 15-40% of triple negative breast tumors have BRCA-related epigenetic down-regulation and increased expression of the inhibitors of BRCA1 function, which have be found to be related to indirect regulation of ID4 oncogene by miR-342. When compared with wholesome breast tissues, miR-21, miR-210 and miR-221 expression are observed to be elevated in the triple-negative breast cancer; whereas expression of miR-10b, miR-145, miR-205, miR-122a, miR-200a/miR-200b, miR-146b and miR-148a are decreased. Interestingly, eight miRNAs are differentially expressed in metastatic breast cancer tissues (miR-200b, miR- 148a, miR-424, miR-125a-5P, miR-627, miR-579, let-7g and miR-101) when compared with the non-metastatic type. The consequence of differential miRNA expression in triple negative breast is a function of target oncogene modulation which may be related to nutritional, environmental and socio-cultural factors. Insights into the risk factors, miRNA and their validated target may provide novel diagnostic tools and treatment options for triple negative breast cancer.