Transcriptome Analysis of MDA-MB-231 Cells Treated with Fumosorinone Isolated from Insect Pathogenic Fungi

In our previous study, we have isolated a new compound, named Fumosorinone (FU) from insect pathogenic fungi, and was found to inhibit proliferation, migration, and invasion of breast cancer MDA-MB-231 cells.

The aim of this study was to identify the underlying molecular mechanisms for FU effects on MDAMB- 231 cells.

After MDA-MB-231 cells were treated with FU for 48h, RNA sequencing was used to identify the effect of FU on the transcriptome of MDA-MB-231 cells. The validation of the relative expression of the selective genes was done using quantitative real-time PCR (qRT-PCR).

The transcriptome results showed that 2733 genes were differentially expressed between the untreated and the FU-treated cells, including 1614 up-regulated and 1119 down-regulated genes. The multiple genes are associated with cancer cell growth, migration, and invasion. Functional analysis identified multitude of pathways related to cancer, such as cell cycle, ECM-receptor interaction, p53 signaling pathway. We selected 4 upregulated and 9 downregulated genes, which are associated with breast cancer to verify their expression using qRT-PCR. The validation showed that HSD3B1, ALOX5, AQP5, COL1A2, CCNB1, CCND1, VCAM-1, PTPN1 and PTPN11 were significantly downregulated while DUSP1, DUSP5, GADD45A, EGR1 were upregulated in FU-treated MDA-MB-231cells.

These aberrantly expressed genes and pathways may play pivotal roles in the anti-cancer activity of FU, and maybe potential targets of FU treatments for TNBC. Further investigations are required to evaluate the FU mechanisms of anti-cancer action in vivo.