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Copyright (c) 2023 Dapeng Wang, Yunyan Li, Fushen Luo, Xue Song, Shuang Wu, Ying Chen, Na Zhang
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Inhibitory Effort of MLN2238 on Basal-Like Breast Cancer: An Investigation Based on the Gene Set Enrichment Analysis
Corresponding Author(s) : Dapeng Wang
Cellular and Molecular Biology,
Vol. 69 No. 7: Issue 7
Abstract
Basal cell-like breast cancer (BLBC), one subtype of breast cancer, has the characteristics of a high recurrence rate and strong invasiveness. Therefore, it is necessary to exploit new drugs for the therapy of BLBC. The data on small molecular drugs were downloaded from the cancer drug sensitivity genomics (GDSC) database, and the target gene information of small molecular drugs was obtained from the SWISS website. Based on the TCGA database, a genome-wide t-value sequencing for screening differentially expressed genes (DEGs) was constructed. The bioinformatics analysis was further performed. The cell cycle was determined using flow cytometry. Western blot was performed to calculate the expression of P21 and P27. siPLK1 transfection was performed to interfere with PLK1 expression. And further cell experimental techniques were performed. The specific effect and mechanisms of the screened small molecular drugs were confirmed through clinical sample studies and in vitro experiments. MLN2238 could significantly inhibit the proliferation of HCC38, a BLBC cell line. The PPI network based on the target gene significantly up-regulated by MLN2238 shows that PLK1 is the key gene, and KEGG analysis shows that the up-regulated target gene is in the cell cycle. Flow cytometry showed that MLN2238 blocked HCC38 cells in the G2/M phase. The results of the Western blot revealed that MLN2238 inhibited the expression of P21 and P27 in HCC38 cells. The survival heat map based on the TCGA database shows that PLK1 has the greatest impact on the survival of breast cancer. Patients with high levels of PLK1 expression had a poorer overall survival rate than those with low levels of PLK1. Cell experiments in vitro revealed that the PLK1 expression decreased significantly after siPLK1 transfection. The ability of cell proliferation was significantly inhibited after SiPLK1 transfection. MLN2238 is a potential target drug for the therapy of BLBC, and PLK1 is the target gene for MLN2238 to inhibit BLBC.
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