Circular RNA circLMO1 Suppresses Cervical Cancer Growth and Metastasis by Triggering miR-4291/ACSL4-Mediated Ferroptosis

作者：Rongying Ou, Shun Lu, Luhui Wang, Yebo Wang, Mingfen Lv, Tian Li, Yunsheng Xu, Jieqiang Lu, Ren‐Shan Ge · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.858598 · 被引用次数：95 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、Immune cells in cancer

Background A number of studies have demonstrated that circular RNA (circRNA) plays a critical role in tumorigenesis and tumor progression. However, the biological effects of most circRNAs on cervical cancer remain unclear. Hsa_circ_0021087 (thereafter named circLMO1) is a circRNA generated from the circularization of exon 2 and exon 3 of LIM Domain Only 1 ( LMO1 ) and first identified as a tumor suppressor in gastric cancer. We aimed to identify the role of circLMO1 in cervical cancer progression. Methods CircLMO1 was verified through qPCR and Sanger sequencing. The biological role of circLMO1 in regulating cervical cancer growth and metastasis was investigated both in vitro and in the nude mouse xenograft tumor model. The dual luciferase reporter assay and rescue experiment were conducted to evaluate the interactions among circLMO1, microRNA (miR)-4291, and acyl-CoA synthetase long chain family member 4 (ACSL4). The role of circLMO1 in regulating ferroptosis was assessed by analyzing lipid reactive oxygen species (ROS), and malonyl dialdehyde (MDA), and glutathione (GSH) content. Results The level of circLMO1 was down-regulated in cervical cancer tissues and was associated with the International Federation of Gynecology and Obstetrics (FIGO) staging. Functionally, circLMO1 overexpression inhibited cervical cancer growth and metastasis both in vitro and in vivo , whereas circLMO1 depletion promoted cervical cancer cell proliferation and invasion. Mechanistically, circLMO1 act...