2. Academic Validation
  3. Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer

Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer

  • Cell Death Dis. 2022 May 20;13(5):479. doi: 10.1038/s41419-022-04943-1.
Tingjia Zhu  # 1,  Yixuan Cen  # 1,  Zhuoye Chen 1,  Yanan Zhang 2,  Lu Zhao 2,  Jiaying Wang 3,  Weiguo Lu 1 2 4,  Xing Xie 1 2,  Xinyu Wang 5 6 7 8
Affiliations

Affiliations

  • 1 Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China.
  • 2 Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China.
  • 3 Department of Obstetrics and Gynecology, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing, China.
  • 4 Cancer center, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
  • 5 Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China. [email protected].
  • 6 Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, Zhejiang, China. [email protected].
  • 7 Cancer center, Zhejiang University, Hangzhou, 310058, Zhejiang, China. [email protected].
  • 8 Department of Gynecology and Obstetrics, The First Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 35595754 DOI: 10.1038/s41419-022-04943-1
Abstract

Circular RNAs (circRNAs) are critical regulators in the occurrence and development of numerous cancers, in which abnormal Autophagy plays a key role. However, the potential involvement of circRNAs in Autophagy is largely unknown. Here, we identified the overexpression of circTICRR, a circular RNA, in cervical Cancer. In vitro experiments showed that knockdown of circTICRR activated Autophagy, and consequently promoted Apoptosis and inhibited proliferation in cervical Cancer cells, and vice versa. CircTICRR interacted with HuR protein via binding to F287/F289 in the RRM3 domain of HuR, stabilizing GLUD1 mRNA and elevating the level of GLUD1 protein. In vivo experiments revealed that knockdown of circTICRR suppressed the growth of transplanted tumors. An inhibitory peptide specific to the binding site between circTICRR and HuR protein promoted Autophagy, induced Apoptosis, suppressed proliferation in cervical Cancer cells, and inhibited the growth of xenografts. Our findings suggest that circTICRR acts as an oncogene in cervical Cancer and the interaction between circTICRR and HuR protein may be a potential target in cervical Cancer therapeutics.

Figures
Products