2. Academic Validation
  3. circMMD reduction following tumor treating fields inhibits glioblastoma progression through FUBP1/FIR/DVL1 and miR-15b-5p/FZD6 signaling

circMMD reduction following tumor treating fields inhibits glioblastoma progression through FUBP1/FIR/DVL1 and miR-15b-5p/FZD6 signaling

  • J Exp Clin Cancer Res. 2023 Mar 17;42(1):64. doi: 10.1186/s13046-023-02642-z.
Shengchao Xu 1 2,  Chengke Luo 1 2,  Dikang Chen 3,  Lu Tang 4,  Quan Cheng 1 2,  Ling Chen 5,  Zhixiong Liu 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Xiangya Hospital, Central South University, No.87, Xiangya Road, Changsha, 410008, Hunan, China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
  • 3 Hunan An Tai Kang Cheng Biotechnology Co., Ltd, Changsha, 410008, China.
  • 4 Department of Anesthesiology, Xiangya Hospital, Central South University, ChangshaHunan, 410008, China.
  • 5 Department of Neurosurgery, Chinese People's Liberation Army of China (PLA) General Hospital, Medical School of Chinese PLA, Institute of Neurosurgery of Chinese PLA, Beijing, 100853, China.
  • 6 Department of Neurosurgery, Xiangya Hospital, Central South University, No.87, Xiangya Road, Changsha, 410008, Hunan, China. zhixiongliu@csu.edu.cn.
  • 7 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. zhixiongliu@csu.edu.cn.
PMID: 36932454 DOI: 10.1186/s13046-023-02642-z
Abstract

Background: Tumor treating fields (TTF) is the latest treatment for GBM. Circular RNA (circRNA) has been demonstrated to play critical roles in tumorigenesis. However, the molecular mechanism of TTF remained largely unknown and the role of circRNA in TTF was not reported. The aim of this study was to elucidate the role and mechanism of circMMD in TTF treatment of GBM.

Methods: Divergent primer was designed to verify the existence of circMMD in GBM cells. The prognostic role of circMMD was explored in glioma specimens. The knockdown and overexpressed plasmids were used to evaluate the effect of circMMD on GBM cell proliferation and TTF efficacy. RNA pull-down and RNA immunoprecipitation were performed to identify binding proteins of circMMD. Subcutaneous and intracranial tumor models were established to validate findings in vivo.

Results: The expression of circMMD was elevated in GBM and its high expression indicated poor prognoses. TTF intervention could reduce circMMD synthesis, which suppressed GBM proliferation and increased TTF-mediated Apoptosis. The reduction of circMMD promoted the interaction between FUBP1 and FIR, which decreased DVL1 transcription. Meanwhile, decreased circMMD would promote the activity of miR-15b-5p to degrade FZD6. Finally, the diminished expression of DVL1 and FZD6 expression suppressed the activation of Wnt/β-catenin pathway.

Conclusions: Our study revealed a novel mechanism of TTF that TTF-mediated reduction of circMMD could inhibit Wnt/β-catenin pathway to suppress GBM proliferation.

Keywords

Glioblastoma; Tumor treating fields; Wnt/β-catenin signaling; circRNA.

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