Exp Mol Med.  2011 May;43(5):298-304. 10.3858/emm.2011.43.5.031.

miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFkappaB1

• Arora H
• Qureshi R
• Jin S
• Park AK
• Park WY

• KMID: 1009969
• DOI: http://doi.org/10.3858/emm.2011.43.5.031

Abstract

The activation of nuclear factor-kappa B1 (NFkappaB1) 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 NFkappaB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in gamma-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFkappaB1. Overexpression of miR-9 down-regulated the level of NFkappaB1 in H1299 cells, and the surviving fraction of gamma-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFkappaB1, although there was no canonical target site for let-7g in the NFkappaB1 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 NFkappaB1.

Keyword

ionizing radiation; let-7g; lung cancer; miR-9; NFkappaB1

MeSH Terms

Base Sequence
Cell Line, Tumor
Cell Survival/genetics/radiation effects
Gene Expression Profiling
*Gene Expression Regulation, Neoplastic/radiation effects
Humans
Lung Neoplasms/genetics/metabolism
MicroRNAs/genetics/*metabolism
NF-kappa B p50 Subunit/genetics/*metabolism
Radiation Tolerance/*genetics
Radiation, Ionizing
Sequence Alignment