Scientists from University of Texas MD Anderson cancer center have revealed that , a unique cell signaling pathway hedgehog, may be the mechanism behind breast cancer metastasis. The study was published in Cell.

Emerging evidence has purported long noncoding RNA (IncRNA) as a new class of players involved in the development and progression of cancer. However, the regulatory roles played by IncRNA in breast-cancer-associated aberrant signaling pathways/transcriptional programs are not completely understood.

In this study, researchers have reported a role for INcRNA BCAR4 in breast cancer metastasis that is mediated by chemokine-induced binding of BCAR4 to two transcription factors with extended regulatory consequences. BCAR4 binding of SNIP and PNUTS in response to CCL21 releases the SNIP1′s inhibition of p300-denpendent histone acetylation, which in turn enables the BCAR4-recruited PNUTS to bind H3K18ac and relieve inhibition of RNA pol Ⅱ via actication of the PP1 phosphatase. This mechanism activates a noncanonical Hedgehog/GLI2 transcriptional program that promotes cell migration. BCAR4 expression correlates with advanced breast cancers, and therapeutic delivery of locked nucleic acids (LNAs) targeting BCAR4 strongly suppresses breast cancer metastasis in mouse models.

Their finding have provided supporting evidence for the regulatory roles played by IncRNA in the progression of aggressive breast cancers. Broadly, the results of the therapeutic effectiveness breast cancer metastasis document an example showing the pharmacologic value of INcRNA in human cancer and other diseases.

Reference:

Xing Z, Lin A, Li C, et al. lncRNA Directs Cooperative Epigenetic Regulation Downstream of Chemokine Signals[J]. Cell, 2014.