title: Role of KCNB1 in the prognosis of gliomas and autophagy modulation.
abstract: Increasing evidence suggests that ion channel genes play an important role in the progression of gliomas. However, the mechanisms by which ion channel genes influence the progression of glioma are not fully understood. We identified KCNB1 as a novel ion gene, associated with malignant progression and favorable overall survival (OS) and progression-free survival (PFS) in glioma patients from three datasets (CGGA, GSE16011 and REMBRANDT). Moreover, we characterized a novel function of autophagy induction accompanied by increased apoptosis and reduced proliferation and invasion of glioma cells for KCNB1. KEGG pathway analysis and in vitro studies suggested that the ERK pathway is involved in KCNB1-mediated regulation of autophagy, which was confirmed by inhibition of KCNB1-induced autophagy by using a selective ERK1/2 inhibitor (U0126) or siERK1/2. In vivo studies showed that KCNB1 induced autophagy while inhibiting tumor growth and increasing survival. Overall, our studies define KCNB1 as a novel prognostic factor for gliomas that exerts its tumor suppressive function through autophagy induction.
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), Beijing, China.|Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.|Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Liang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yong-Yi
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. wyz232@163.com.|Chinese Glioma Cooperative Group (CGCG), Beijing, China. wyz232@163.com.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. wyz232@163.com.
authors.forename: Yong-Zhi
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. shizhong_zh@163.com.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. shizhong_zh@163.com.
authors.forename: Shi-Zhong
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D066264:Datasets as Topic; D018572:Disease-Free Survival; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011379:Prognosis; D051669:Shab Potassium Channels / Q000235:genetics*
chemical_list: D002070:Butadienes; C496988:KCNB1 protein, human; D009570:Nitriles; D051669:Shab Potassium Channels; C113580:U 0126