Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

by Selleckchem | Nov 30 2023

Altered expression of circular RNAs (circRNAs) has previously been investigated in breast cancer. However, little is known about the effects of drugs on their regulation and relationship with the cognate linear transcript (linRNA). We analyzed the dysregulation of both 12 cancer-related circRNAs and their linRNAs in two breast cancer cell lines undergoing various treatments. We selected 14 well-known anticancer agents affecting different cellular pathways and examined their impact. Upon drug exposure circRNA/linRNA expression ratios increased, as a result of the downregulation of linRNA and upregulation of circRNA within the same gene. In this study, we highlighted the relevance of identifying the drug-regulated circ/linRNAs according to their oncogenic or anticancer role. Interestingly, VRK1 and MAN1A2 were increased by several drugs in both cell lines. However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells.

Comments:

It seems like you're summarizing a research study or scientific article related to the investigation of circular RNAs (circRNAs) in breast cancer and their response to various anticancer drugs. The study delves into the dysregulation of specific cancer-related circRNAs and their corresponding linear transcripts (linRNAs) in breast cancer cell lines when exposed to different anticancer agents.

Here's a breakdown of the key points in your summary:

1. **Background**: Previous research has explored the role of circRNAs in breast cancer. However, the effects of drugs on circRNA regulation and their relationship with linRNAs remain poorly understood.

2. **Study Design**: The study analyzed the dysregulation of 12 cancer-related circRNAs and their linRNAs in two breast cancer cell lines under different drug treatments. Fourteen well-known anticancer agents, targeting various cellular pathways, were selected for examination.

3. **Findings**:
   - **CircRNA/LinRNA Expression Ratios**: Upon exposure to drugs, the study observed an increase in circRNA/linRNA expression ratios. This was due to the downregulation of linRNA and upregulation of circRNA within the same gene.
   - **Identification of Drug-Regulated circRNAs/LinRNAs**: The study highlighted the importance of identifying drug-regulated circRNAs and linRNAs based on their roles in either promoting or inhibiting cancer.
   - **Specific CircRNAs and Drugs**:
     - **VRK1 and MAN1A2**: These genes were increased by several drugs in both cell lines. However, they had opposite effects; circ/linVRK1 favored apoptosis, while circ/linMAN1A2 stimulated cell migration. XL765 was the only drug that did not alter the ratio of other dangerous circ/linRNAs in MCF-7.
     - **AMG511 and GSK1070916**: These drugs decreased circGFRA1 in MDA-MB-231 cells, indicating a positive response to the treatment.
   - **Association with Mutated Pathways**: Certain circRNAs were associated with specific mutated pathways, such as the PI3K/AKT pathway in MCF-7 cells and the NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells. Circ/linHIPK3 correlated with cancer progression and drug resistance in MCF-7 cells.

4. **Conclusion**: The study emphasizes the importance of understanding the regulatory mechanisms of circRNAs and linRNAs in response to anticancer drugs. It also highlights the potential of specific circRNAs as biomarkers or therapeutic targets in breast cancer treatment.

This research provides valuable insights into the intricate relationship between circRNAs, linRNAs, and their response to anticancer drugs in breast cancer, paving the way for further studies and potential therapeutic interventions.