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Published on: January 30, 2018
miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1
Himanshu Arora1, Rehana Qureshi, Shunzi Jin
1Laboratory of Molecular and Genomic Medicine, Department of Biomedical Sciences, Seoul National University College of Medicine, Korea.
Abstract:
The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.
Insights
MicroRNAs miR-9 and let-7g can enhance lung cancer radiotherapy by suppressing nuclear factor-kappa B1 (NFkB1). This inhibition increases cancer cell sensitivity to ionizing radiation (IR), improving treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Nuclear factor-kappa B1 (NFkB1) activation in cancer cells can lead to resistance against ionizing radiation (IR).
- Enhancing radiosensitivity is crucial for improving lung cancer treatment efficacy.
Purpose of the Study:
- To identify microRNAs (miRNAs) that suppress NFkB1.
- To evaluate the impact of these miRNAs on radiosensitivity in lung cancer cells.
Main Methods:
- Screening of miRNAs targeting NFkB1 in γ-irradiated H1299 human lung cancer cells.
- Analysis of miRNA and NFkB1 expression using time-series data.
- Overexpression of candidate miRNAs (miR-9, let-7g) to assess NFkB1 levels and cell survival post-irradiation.
Main Results:
- miR-9 expression was inversely correlated with NFkB1 levels in irradiated lung cancer cells.
- Overexpression of miR-9 led to decreased NFkB1 levels and reduced cell survival after γ-irradiation.
- let-7g also suppressed NFkB1 expression, despite lacking a canonical binding site.
Conclusions:
- miR-9 and let-7g can enhance the therapeutic efficiency of radiotherapy for lung cancer.
- Inhibition of NFkB1 by these miRNAs contributes to increased radiosensitivity.
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