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Title: miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway

Abstract

Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealed in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate thatmore » miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.« less

Authors:
 [1];  [2];  [3]; ; ; ;  [1];  [1]
  1. Radiation Oncology Department, PLA Airforce General Hospital, Beijing (China)
  2. (China)
  3. Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin (China)
Publication Date:
OSTI Identifier:
22423841
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 91; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMAL TISSUES; APOPTOSIS; CORRELATIONS; LUCIFERASE; LUNGS; MICE; NEOPLASMS; POTENTIALS; RADIOSENSITIVITY; RECEPTORS

Citation Formats

Lan, Fengming, Radiation Oncology Department, Tianjin Hospital, Tianjin, Yue, Xiao, Ren, Gang, Li, Hongqi, Ping, Li, Wang, Yingjie, and Xia, Tingyi, E-mail: xiatingyi1959@163.com. miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2014.09.021.
Lan, Fengming, Radiation Oncology Department, Tianjin Hospital, Tianjin, Yue, Xiao, Ren, Gang, Li, Hongqi, Ping, Li, Wang, Yingjie, & Xia, Tingyi, E-mail: xiatingyi1959@163.com. miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway. United States. doi:10.1016/J.IJROBP.2014.09.021.
Lan, Fengming, Radiation Oncology Department, Tianjin Hospital, Tianjin, Yue, Xiao, Ren, Gang, Li, Hongqi, Ping, Li, Wang, Yingjie, and Xia, Tingyi, E-mail: xiatingyi1959@163.com. Thu . "miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway". United States. doi:10.1016/J.IJROBP.2014.09.021.
@article{osti_22423841,
title = {miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway},
author = {Lan, Fengming and Radiation Oncology Department, Tianjin Hospital, Tianjin and Yue, Xiao and Ren, Gang and Li, Hongqi and Ping, Li and Wang, Yingjie and Xia, Tingyi, E-mail: xiatingyi1959@163.com},
abstractNote = {Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealed in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate that miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.},
doi = {10.1016/J.IJROBP.2014.09.021},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 91,
place = {United States},
year = {Thu Jan 01 00:00:00 EST 2015},
month = {Thu Jan 01 00:00:00 EST 2015}
}