EDITGENE KO cells Decode SETD7 Regulation of TNBC Cell Migration and EMT Process Mechanism

Recently in October, the Gao Lili team at Shanghai University of Science and Technology published an original article in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (IF: 6.2). It was entitled ‘SETD7 promotes metastasis of triple-negative breast cancer by YY1 lysine methylation’ and the used SETD7 gene knockout cells was from EDITGENE. This article clarified the molecular mechanism of SETD7 regulating TNBC cell migration and EMT process through the ERK/MAPK signaling pathway through a series of studies.

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The authors conducted experiments of silence and overexpress of SETD7 in MDA-MB-231 cells and Hs578T cells respectively. Through transwell experiments and wound healing experiments, they investigated SETD7 effection on cell migration. Compared with the NC group, overexpression of SETD7 significantly enhanced the cell migration of these two TNBC cell lines. In order to explore the mechanism of SETD7 affecting TNBC migration, sequencing and Western blot experiments demonstrated that overexpression of SETD7 promoted TNBC migration, and EMT may be mediated by the ERK/MAPK signaling pathway.

Further experiments revealed that the stability of transcription factor YY1 in SETD7-KO cells was reduced, but less affected in SETD7-OE cells. The level of polyubiquitinated YY1 in SETD7-KO cells was higher,which confirmed that SETD7-mediated ubiquitination of YY1 regulates its protein expression level and stability.

To investigate whether TNBC cell migration is regulated by SETD7 and whether EMT is dependent on YY1, the authors overexpressed YY1 in TNBC cells containing SETD7-KO and knocked out YY1 in SETD7-OE cells. The results showed that without SETD7, YY1 restored cell migration in MDA-MB-231 cells, while in the SETD7-overexpressed Hs578T cells, YY1-KD disrupted cell migration. In addition, overexpression of YY1 in SETD7-KO cells restored the ERK/MAPK pathway and EMT, but YY1-KD inhibited the ERK/MAPK pathway and EMT induced by SETD7-OE.

The results indicated that the SET/YY1/ERK/MAPK pathway played an important role in inducing the migration and EMT of TNBC cells.

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