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.
Highlights
Thyroid cancer remains the most frequent endocrine system tumor with an increasing rate in multiple regions and countries [1, 2]
The silencing of circ_0067934 increased the levels of ferroptosisrelated markers, including Fe2+, iron, and reactive oxygen species (ROS), in FTC133 and TPC-1 cells (Figures 1E–G), and the treatment of erastin served as a positive control, suggesting that circ_0067934 inhibits the thyroid cancer cell ferroptosis
The overexpression of circ_0067934 reduced the levels of ferroptosis-related markers, including Fe2+, iron, and ROS, in FTC133 and TPC-1 cells (Figures S1D–F), and the treatment of erastin served as a positive control, confirming that circ_0067934 inhibits the thyroid cancer cell ferroptosis
Summary
Thyroid cancer remains the most frequent endocrine system tumor with an increasing rate in multiple regions and countries [1, 2]. Thyroid cancer can be histologically classified as anaplastic thyroid cancer (ATC), medullary thyroid cancer (MTC), follicular thyroid cancer (FTC), and papillary thyroid cancer (PTC) [3]. Though PTC presents a favorable prognosis, there are yet 10%–20% of thyroid cancer patients have the features of recurrence, drug resistance, distant metastasis, and local invasion, leading to a low survival time [4, 5]. Ferroptosis is a complicated process of programmed cell death distinct from apoptosis and autophagy [6, 7]. Ferroptosis can be activated by some stimulator, including erastin, and is characterized by the accumulation of ROS and iron [8, 9]. Ferroptosis is involved in the pathogenesis of various cancers [10], but the regulation mechanism of ferroptosis in thyroid cancer is elusive
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