title: c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro.
abstract: c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Otology, Jinan, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Otology, Jinan, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Fuping
authors.initials: F
authors.lastname: Qian
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Daogong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Han
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Otology, Jinan, China.
authors.forename: Gaoying
authors.initials: G
authors.lastname: Sun
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Qi
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Tang
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Otology, Jinan, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.|Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, Southeast University, Nanjing 210096, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chai
authors.affiliation: Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Otology, Jinan, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D020598:Proto-Oncogene Proteins c-myb / Q000037:antagonists & inhibitors / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D011500:Protein Synthesis Inhibitors; D020598:Proto-Oncogene Proteins c-myb; D017382:Reactive Oxygen Species; D009355:Neomycin