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

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          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 Fe 2+, 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.

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          Most cited references34

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          FSP1 is a glutathione-independent ferroptosis suppressor

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            Recent Progress in Ferroptosis Inducers for Cancer Therapy

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              Thyroid cancer

              Thyroid cancer is the fifth most common cancer in women in the USA, and an estimated over 62 000 new cases occurred in men and women in 2015. The incidence continues to rise worldwide. Differentiated thyroid cancer is the most frequent subtype of thyroid cancer and in most patients the standard treatment (surgery followed by either radioactive iodine or observation) is effective. Patients with other, more rare subtypes of thyroid cancer-medullary and anaplastic-are ideally treated by physicians with experience managing these malignancies. Targeted treatments that are approved for differentiated and medullary thyroid cancers have prolonged progression-free survival, but these drugs are not curative and therefore are reserved for patients with progressive or symptomatic disease.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                05 July 2021
                2021
                : 12
                : 670031
                Affiliations
                [1] 1 Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University , Harbin, China
                [2] 2 Department of Endocrinology, Qiqihar First Hospital , Qiqihar, China
                [3] 3 Affiliated Qiqihar Hospital, Southern Medical University , Qiqihar, China
                Author notes

                Edited by: Veronica Vella, University of Catania, Italy

                Reviewed by: De Jun Ding, Weifang Medical University, China; Lin Wang, Xi’an International University, China

                *Correspondence: Xiao-Rong Zhan, zhandywib431@ 123456163.com

                This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2021.670031
                8287831
                34290668
                32d6160e-8564-4da5-85fb-8ac5f4e81bb8
                Copyright © 2021 Wang, Ma and Zhan

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 February 2021
                : 18 May 2021
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 34, Pages: 10, Words: 3623
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                thyroid cancer,ferroptosis,circ_0067934,mir-545-3p,slc7a11
                Endocrinology & Diabetes
                thyroid cancer, ferroptosis, circ_0067934, mir-545-3p, slc7a11

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