title: IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy.
abstract: Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: J-H
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: X
authors.initials: X
authors.lastname: Long
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shuai
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wei
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Duran
authors.affiliation: Department of Anatomical & Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: K-W
authors.initials: KW
authors.lastname: Lo
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: S W
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Glaser
authors.affiliation: School of Life Sciences, Central South University, Hunan 410008, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: X
authors.initials: X
authors.lastname: Feng
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Xiangya Hospital, Central South University, Hunan 410008, China.|Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: J-L
authors.initials: JL
authors.lastname: Luo