2. Academic Validation
  3. Hypoxia-induced circADAMTS6 in a TDP43-dependent manner accelerates glioblastoma progression via ANXA2/ NF-κB pathway

Hypoxia-induced circADAMTS6 in a TDP43-dependent manner accelerates glioblastoma progression via ANXA2/ NF-κB pathway

  • Oncogene. 2022 Nov 17. doi: 10.1038/s41388-022-02542-0.
Shulin Zhao 1 2,  Boyan Li 1 2,  Rongrong Zhao 1 2,  Ziwen Pan 1 2,  Shouji Zhang 1 2,  Wei Qiu 1 2,  Qindong Guo 1 2,  Yanhua Qi 1 2,  Zijie Gao 1 2,  Yang Fan 1 2,  Hao Xu 2 3,  Ming Li 2 4,  Jian Zhang 2 5,  Huizhi Wang 1 2,  Jianye Xu 1 2,  Shaobo Wang 1 2,  Qingtong Wang 1 2,  Jiawei Qiu 1 2,  Lin Deng 1 2,  Xing Guo 1 2,  Ping Zhang 1 2,  Hao Xue 6 7,  Gang Li 8 9
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China.
  • 2 Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China.
  • 3 Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • 4 Department of Neurosurgery, Taian Central Hospital, Taian, Shandong, China.
  • 5 Department of Neurosurgery, Dezhou People's Hospital, Dezhou, China.
  • 6 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China. [email protected].
  • 7 Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China. [email protected].
  • 8 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, Shandong, China. [email protected].
  • 9 Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China. [email protected].
PMID: 36396726 DOI: 10.1038/s41388-022-02542-0
Abstract

Circular RNAs (circRNAs) play important roles in the malignant progression of tumours. Herein, we identified an unreported circRNA (hsa-circ-0072688, also named circADAMTS6) that is specifically upregulated in the hypoxic microenvironment of glioblastoma and closely correlated with poor prognosis of gliblastoma patients. We found that circADAMTS6 promotes the malignant progression of glioblastoma by promoting cell proliferation and inhibiting Apoptosis. Mechanistically, the hypoxic tumour microenvironment upregulates circADAMTS6 expression through transcription factor activator protein 1 (AP-1) and RNA-binding protein TAR DNA-binding protein 43 (TDP43). Moreover, circADAMTS6 accelerates glioblastoma progression by recruiting and stabilising annexin A2 (ANXA2) in a proteasomes-dependent manner. Furthermore, we found T-5224 (AP-1 Inhibitor) treatment induces downregulation of circADAMTS6 and then inhibits tumour growth. In conclusion, our findings highlight the important role of the circADAMTS6/ANXA2 axis based on hypoxic microenvironment in glioblastoma progression, as well as its regulation in NF-κB pathway. Targeting circADAMTS6 is thus expected to become a novel therapeutic strategy for glioblastoma.

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Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-12270
    99.59%, c-Fos/AP-1 Inhibitor