Circular RNA Circ_0067934 Attenuates Ferroptosis of Thyroid Cancer Cells by miR-545-3p/SLC7A11 Signaling

Front Endocrinol (Lausanne). 2021 Jul 5:12:670031. doi: 10.3389/fendo.2021.670031. eCollection 2021.

Abstract

Ferroptosis is an emerging programmed cell death distinguished from apoptosis and autophagy and plays essential roles in tumorigenesis. Thyroid cancer is a prevalent endocrine tumor, but the molecular mechanism of ferroptosis during thyroid cancer development remains unclear. Here, we identified the critical function of circular RNA circ_0067934 in repressing ferroptosis of thyroid cancer cells. Our data showed that the ferroptosis activator erastin decreased thyroid cancer cell viabilities, while the circ_0067934 shRNA further attenuated erastin-inhibited cell viabilities. The silencing of circ_0067934 enhanced the levels of ferroptosis-related markers, including Fe2+, iron, and ROS in the cells. The knockdown of circ_0067934 induced thyroid cancer cell apoptosis and repressed thyroid cancer cell proliferation in vitro and in vivo. Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation. Therefore, we concluded that Circ_0067934 attenuated ferroptosis of thyroid cancer cells by miR-545-3p/SLC7A11 signaling. Circ_0067934 may serve as a potential therapeutic target by regulating ferroptosis for the treatment of thyroid cancer.

Keywords: SLC7A11; circ_0067934; ferroptosis; miR-545-3p; thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / metabolism*
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Ferroptosis*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Amino Acid Transport System y+
  • Biomarkers, Tumor
  • MIR545 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • SLC7A11 protein, human