The effect of ribociclib on the expression levels of miR-141 and CDK4/6-USP51 signaling pathway genes in MCF-7 and MDA-MB-231 cells.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Purines*/pharmacology ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Aminopyridines*/pharmacology ; Cyclin-Dependent Kinase 6*/genetics ; Cyclin-Dependent Kinase 6*/metabolism ; Cyclin-Dependent Kinase 4*/genetics ; Cyclin-Dependent Kinase 4*/metabolism ; Gene Expression Regulation, Neoplastic*/drug effects ; Signal Transduction*/drug effects; Humans ; Female ; MCF-7 Cells ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Breast Neoplasms/genetics ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; MDA-MB-231 Cells

Introduction: Patients with breast cancer, especially triple-negative breast cancer, have a poor prognosis. There is still no effective treatment for this disease. Due to resistance to traditional treatments such as chemotherapy and radiation therapy, there is a need to discover novel treatment strategies to treat this disease. Ribociclib is a selective CDK4/6 inhibitor. Approximately 20% of patients with HR+ breast cancer developed primary resistance to CDK4/6 inhibitors, and more than 30% experienced secondary resistance. Since most patients experience resistance during CDK4/6 inhibitor treatment, managing this disease is becoming more challenging. Many malignant tumors abnormally express microRNA (miR)-141, which participates in several cellular processes, including drug resistance, proliferation, epithelial-mesenchymal transition, migration, and invasion.
Materials and Methods: In the present study, we cultured MDA-MB-231 and MCF-7 cells in DMEM-F12 medium. By performing MTT assay we determined the cytotoxic effects of ribociclib on breast cancer cells, as well as determining the IC50 of it. Then, we treated the cells with ribociclib at two time points: 24 h and 72 h. After that, RNA was isolated and reverse transcribed to cDNA. Finally, we performed qRT‒PCR to evaluate how ribociclib affects the expression level of desired genes.
Results and Conclusion: We found that ribociclib can inhibit cell growth in a dose- and time-dependent manner. We examined the mRNA expression of 4 genes. After ribociclib treatment, the mRNA expression of CDK6 and MYH10 decreased (p < 0.01, p < 0.05). The mRNA expression of CDON increased (p<0.05), but no significant changes were observed in ZEB1 mRNA expression. Furthermore, the qRT‒PCR results for miR-141 showed that the expression of miR-141 increased (p<0.01) after 72 h of treatment with ribociclib.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Baghermanesh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Purines)
TK8ERE8P56 (ribociclib)
0 (MicroRNAs)
0 (Aminopyridines)
EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
EC 2.7.11.22 (CDK4 protein, human)
EC 2.7.11.22 (CDK6 protein, human)

Date Created: 20240828 Date Completed: 20240828 Latest Revision: 20240831

20240831

PMC11355560

10.1371/journal.pone.0309289

39196911