IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

 

Recently, long noncoding RNA (IncRNA) has been reported as a novel factor related to generation and progression of cancer. However, the precise roles of IncRNAs in regulation of breast cancer are not fully understood. Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. The article was published on Cell.

 

The study showed the role of BCAR4 in breast cancer metastasis was regulated by the bindings of BCAR4 with two coordinated proteins, smad nuclear-interacting protein 1 (SNIP1), and serine/threonine-protein phspharase 1 regulatory subunit 10 (PNUTS). The binding of BCAR4 and SNIP1 leads to the acetylation of H3K18ac by p300 histone acetylatransferase. H3K18ac locates on the promoters of transcription units targeted by glioma-associated oncogene homolog 2 (GLI2), which is a transcription factor related to breast cancer regulation. The acetylated H3K18 can be recognized and bond by BCAR4-recruited PNUTS, leading to a recruitment of the promoters of GLI2 target genes. This process diminishes inhibition of RNA polymerase II, and activates a cell-migration-related pathway, noncanonical Hedgehog/GLI2 signaling pathway.

 

Furthermore, researchers provides evidences that the expression level of BCAR4 is positively correlated to the metastatic potential of breast cancer patients, and the treatment of locked nucleic acids (LNAs), targeting BCAR4, significantly suppresses breast cancer metastasis in animal models. The results reveal a mechanism of IncRNA in regulating breast cancer metastasis, and show the therapeutic potential of medicines targeting IncRNA in human cancer or other diseases.

 

Reference:
Cell. 2014 Nov 20;159(5):1110-25.

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