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Updated: Aug 14, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Targeting miR-5088-5p attenuates radioresistance by suppressing Slug
Hyun Jeong Seok1, Jae Yeon Choi1, Joo Mi Yi2
1Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
Abstract:
Radiotherapy is widely used for cancer treatment, but paradoxically, it has been reported that surviving cancer cells can acquire resistance, leading to recurrence or metastasis. Efforts to reduce radioresistance are required to increase the effectiveness of radiotherapy. miRNAs are advantageous as therapeutic agents because it can simultaneously inhibit the expression of several target mRNAs. Therefore, this study discovered miRNA that regulated radioresistance and elucidated its signaling mechanism. Our previous study confirmed that miR-5088-5p was associated with malignancy and metastasis in breast cancer. As a study to clarify the relationship between radiation and miR-5088-5p identified as onco-miRNA, it was confirmed that radiation induced hypomethylation of the promoter of miR-5088-5p and its expression increased. On the other hand, miR-5088-5p inhibitors were confirmed to reduce radiation-induced epithelial-mesenchymal transition, stemness, and metastasis by reducing Slug. Therefore, this study showed the potential of miR-5088-5p inhibitors as therapeutic agents to suppress radioresistance.
Insights
This study reveals that miR-5088-5p promotes cancer radioresistance by increasing Slug expression after radiation. Inhibiting miR-5088-5p can overcome this resistance, offering a new therapeutic strategy for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Radiotherapy is a cornerstone of cancer treatment, but acquired radioresistance in surviving cancer cells often leads to recurrence and metastasis.
- MicroRNAs (miRNAs) are potent regulators of gene expression and are being explored as therapeutic agents due to their ability to target multiple mRNAs simultaneously.
- Reducing radioresistance is crucial for enhancing the efficacy of radiotherapy.
Purpose of the Study:
- To identify miRNAs that regulate radioresistance and elucidate their underlying signaling mechanisms.
- To investigate the role of miR-5088-5p, previously linked to breast cancer malignancy and metastasis, in the context of radiotherapy.
- To explore the therapeutic potential of miR-5088-5p inhibitors in overcoming radioresistance.
Main Methods:
- Investigated the effect of radiation on miR-5088-5p expression and its promoter methylation status.
- Utilized miR-5088-5p inhibitors to assess their impact on radiation-induced cellular changes.
- Quantified the reduction of Slug expression following miR-5088-5p inhibition.
Main Results:
- Radiation exposure was found to induce hypomethylation of the miR-5088-5p promoter, leading to increased miR-5088-5p expression.
- Inhibition of miR-5088-5p significantly reduced radiation-induced epithelial-mesenchymal transition, stemness, and metastasis.
- The observed effects were associated with a reduction in Slug, a key regulator of these processes.
Conclusions:
- miR-5088-5p acts as an onco-miRNA that promotes radioresistance in cancer cells.
- Radiation therapy can upregulate miR-5088-5p through promoter hypomethylation.
- miR-5088-5p inhibitors demonstrate potential as therapeutic agents to overcome radioresistance by targeting the Slug pathway.
