Transcriptomic Changes in Cisplatin-Resistant MCF-7 Cells

Author:

Ruiz-Silvestre Araceli12ORCID,Garcia-Venzor Alfredo3,Ceballos-Cancino Gisela4ORCID,Sánchez-López José M.1ORCID,Vazquez-Santillan Karla5ORCID,Mendoza-Almanza Gretel16ORCID,Lizarraga Floria1ORCID,Melendez-Zajgla Jorge4ORCID,Maldonado Vilma1ORCID

Affiliation:

1. Laboratorio de Epigenetica, Instituto Nacional de Medicina Genomica (INMEGEN), Ciudad de Mexico 14610, Mexico

2. Posgrado en Ciencias Biomédicas, Universidad Nacional Autónoma de Mexico (UNAM), Ciudad de Mexico 04510, Mexico

3. Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel

4. Laboratorio de Genomica Funcional del Cancer, Instituto Nacional de Medicina Genomica (INMEGEN), Ciudad de Mexico 14610, Mexico

5. Laboratorio de Innovación en Medicina de Precisión, Instituto Nacional de Medicina Genomica (INMEGEN), Ciudad de Mexico 14610, Mexico

6. Consejo Nacional de Ciencia y Tecnologia, Ciudad de Mexico 03940, Mexico

Abstract

Breast cancer is a leading cause of cancer-related deaths among women. Cisplatin is used for treatment, but the development of resistance in cancer cells is a significant concern. This study aimed to investigate changes in the transcriptomes of cisplatin-resistant MCF7 cells. We conducted RNA sequencing of cisplatin-resistant MCF7 cells, followed by differential expression analysis and bioinformatic investigations to identify changes in gene expression and modified signal transduction pathways. We examined the size and quantity of extracellular vesicles. A total of 724 genes exhibited differential expression, predominantly consisting of protein-coding RNAs. Notably, two long non-coding RNAs (lncRNAs), NEAT1 and MALAT, were found to be dysregulated. Bioinformatic analysis unveiled dysregulation in processes related to DNA synthesis and repair, cell cycle regulation, immune response, and cellular communication. Additionally, modifications were observed in events associated with extracellular vesicles. Conditioned media from resistant cells conferred resistance to wild-type cells in vitro. Furthermore, there was an increase in the number of vesicles in cisplatin-resistant cells. Cisplatin-resistant MCF7 cells displayed differential RNA expression, including the dysregulation of NEAT1 and MALAT long non-coding RNAs. Key processes related to DNA and extracellular vesicles were found to be altered. The increased number of extracellular vesicles in resistant cells may contribute to acquired resistance in wild-type cells.

Funder

CONACYT

National Institute of Medicine Genomic

Publisher

MDPI AG

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