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Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4
Huyen Trang Ha Thi1, Hye-Yeon Kim1, Young-Mi Kim2
1Laboratory of Cancer Cell Biology, Department of Biochemistry, Gachon University School of Medicine, Incheon 21999, Republic of Korea.
Abstract:
Radioresistance poses a major challenge in the treatment of advanced rectal cancer. Therefore, understanding the detailed mechanisms of radioresistance may improve patient response to irradiation and the survival rate. To identify the novel targets that modulate the radiosensitivity of rectal cancer, we performed small RNA sequencing with human rectal cancer cell lines. Through bioinformatics analysis, we selected microRNA-310a (miR-130a) as a promising candidate to elucidate radioresistance. miR-130a was dramatically upregulated in radiosensitive rectal cancer cells and overexpression of miR-130a promotes rectal cancer cell radiosensitivity. Mechanically, miR-130a reversed the epithelial-mesenchymal transition phenotype of rectal cancer cells following inhibition of cell invasion upon irradiation. Moreover, miR-130a also inhibited the repair of irradiation-induced DNA damage followed by cell death. We identified that SOX4 was a direct target of miR-130a. Overexpression of SOX4 reversed the promotion activity of miR-130a on radiosensitivity. Together, our findings suggest that miR-130a functions as a radiosensitizer in rectal cancer and reveals a potential therapeutic target and preoperative prognostic marker for radiotherapy.
Insights
MicroRNA-310a (miR-130a) enhances rectal cancer radiosensitivity by inhibiting DNA damage repair and epithelial-mesenchymal transition. This microRNA represents a potential therapeutic target for improving radiotherapy outcomes.
Area of Science:
- Molecular Oncology
- Cancer Therapeutics
- Radiotherapy Research
Background:
- Radioresistance is a significant obstacle in advanced rectal cancer treatment, limiting therapeutic efficacy.
- Understanding the molecular mechanisms underlying radioresistance is crucial for improving patient survival rates.
- Novel molecular targets are needed to enhance the sensitivity of rectal cancer cells to radiation therapy.
Purpose of the Study:
- To identify novel molecular targets that modulate the radiosensitivity of human rectal cancer cells.
- To elucidate the role and mechanism of microRNA-310a (miR-130a) in rectal cancer radioresistance.
Main Methods:
- Small RNA sequencing was performed on human rectal cancer cell lines.
- Bioinformatics analysis was used to identify candidate microRNAs.
- Functional studies involved miR-130a overexpression, assessment of epithelial-mesenchymal transition, DNA damage repair inhibition, and SOX4 target validation.
Main Results:
- MicroRNA-310a (miR-130a) was significantly upregulated in radiosensitive rectal cancer cells.
- Overexpression of miR-130a enhanced rectal cancer cell radiosensitivity by reversing epithelial-mesenchymal transition and inhibiting DNA damage repair.
- SOX4 was identified as a direct target of miR-130a, and its overexpression counteracted the radiosensitizing effects of miR-130a.
Conclusions:
- MicroRNA-310a (miR-130a) acts as a radiosensitizer in rectal cancer, promoting cell death after irradiation.
- miR-130a represents a potential therapeutic target for overcoming radioresistance in rectal cancer.
- miR-130a may serve as a preoperative prognostic marker for radiotherapy response in rectal cancer patients.
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