Neurokinin 1 (NK1) encodes full-length (NK1-FL) and truncated (NK1-Tr) receptors, with distinct 3′ UTR. NK1-Tr exerts oncogenic functions and is increased in breast cancer (BC). Enhanced transcription of NK1 resulted in higher level of NK1-Tr. The 3′ UTR of these two transcripts are distinct with NK1-Tr terminating at a premature stop codon. NK1-Tr mRNA gained an advantage over NK1-FL with regards to translation. This is due to the ability of miR519B to interact with sequences within the 3′ UTR of NK1-FL, but not NK1-Tr since the corresponding region is omitted. MiR519b suppressed the translation of NK1-FL in T47D and MDA-MB-231 resulting increased NK1-Tr protein. Cytokines can induce the transcription of NK1. However, our studies indicated that translation appeared to be independent of cytokine production by the BC cells (BCCs). This suggested that transcription and translation of NK1 might be independent. The findings were validated in vivo. MiR-519b suppressed the growth of MDA-MB-231 in 7/10 nude BALB/c. In total, increased NK1-Tr in BCCs is due to enhanced transcription and suppressed translation of NK1-FL by miR-519b to reduced tumor growth. In summary, we report on miRNA as a method to further regulate the expression of a spiced variant to promote oncogenesis. In addition, the findings have implications for therapy with NK1 antagonists. The oncogenic effect of NK1-Tr must be considered to improve the efficacy of current drugs to NK1.
Despite recent advances in the diagnoses and treatment of breast cancer, this disease continues to be a major cause of death. One of the biggest challenges in breast cancer treatment is bone metastasis. Breast cancer cells (BCCs) are capable of migrating to the bone marrow and utilizing the marrow microenvironment to remain quiescent. While exhibiting quiescence in the marrow, BCCs can evade the effects of conventional cancer treatments such as chemotherapy. Therefore, scientists must find a new paradigm to target these quiescent BCCs. The development of potential targets may require a more comprehensive understanding of the marrow microenvironment and its regulators. The preprotachykinin-1 (PPT-I) gene encodes for the tachykinin peptides, which interact with neurokinin (NK) receptors. Studies have correlated this interaction with BCC integration into the bone marrow and breast cancer progression. In this review, we discuss the roles that different factors of the marrow microenvironment play in breast cancer and targets of NK receptors as potential treatment options.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.