title: miR-15a/16 enhances radiation sensitivity of non-small cell lung cancer cells by targeting the TLR1/NF-κB signaling pathway.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China; Radiation Oncology Department, Tianjin Hospital, Tianjin, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Lan
authors.affiliation: Tianjin Huanhu Hospital, Tianjin Neurosurgery Institute, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Li
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ping
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Radiation Oncology Department, PLA Airforce General Hospital, Beijing, China. Electronic address: xiatingyi1959@163.com.
authors.forename: Tingyi
authors.initials: T
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D015536:Down-Regulation; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*; D011897:Random Allocation; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D051194:Toll-Like Receptor 1; D008156:Luciferases