Upregulated AHIF-mediated radioresistance in glioblastoma

Keman Liao; Xiumei Ma; Binghong Chen; Xiaojie Lu; Yaomin Hu; Yingying Lin; Renhua Huang; Yongming Qiu

doi:10.1016/j.bbrc.2018.12.136

Upregulated AHIF-mediated radioresistance in glioblastoma

Biochem Biophys Res Commun. 2019 Feb 5;509(2):617-623. doi: 10.1016/j.bbrc.2018.12.136. Epub 2018 Dec 31.

Authors

Keman Liao¹, Xiumei Ma², Binghong Chen¹, Xiaojie Lu³, Yaomin Hu⁴, Yingying Lin¹, Renhua Huang⁵, Yongming Qiu⁶

Affiliations

¹ Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Department of Radiation, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
³ Department of Neurosurgery, Wuxi No.2 Hospital Affiliated to Nanjing Medical University, Wuxi, China.
⁴ Department of Endocrinology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁵ Department of Radiation, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China; Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: huangrenhua_hrh@126.com.
⁶ Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. Electronic address: qiuzhoub@126.com.

PMID: 30606477
DOI: 10.1016/j.bbrc.2018.12.136

Abstract

Long non-coding RNAs (lncRNAs) play vital roles in the pathobiology of glioblastoma multiforme (GBM). Though radiotherapy remains the most effective component of multiple therapies for patients with GBM, lncRNAs conferring GBM radioresistance are less unknown. Here, the present study identified that the antisense transcript of hypoxia-inducible factor-1α (AHIF) was upregulated in GBM cells after radiotherapy. The deregulation of AHIF affected GBM cell clonogenic formation, DNA repair and apoptosis. Notably, knockdown of AHIF inhibited tumorigenesis after radiotherapy in vivo. Further biochemical analysis identified that AHIF regulated proteins associated with apoptosis after radiotherapy. Thus, the present data illustrate that suppression of AHIF increases radiosensitivity in GBM cells, which may be a potential diagnostic and therapeutic target for GBM patients.

Keywords: AHIF; Apoptosis; Glioblastoma; Radiotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / radiation effects
Brain Neoplasms / genetics*
Brain Neoplasms / radiotherapy*
Cell Line, Tumor
Gene Expression Regulation, Neoplastic / radiation effects
Glioblastoma / genetics*
Glioblastoma / radiotherapy*
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
Mice
RNA, Long Noncoding / genetics*
Radiation Tolerance
Up-Regulation* / radiation effects

Substances

Hypoxia-Inducible Factor 1, alpha Subunit
RNA, Long Noncoding