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Circular RNA RHBDD1 regulates tumorigenicity and ferroptosis in colorectal cancer by mediating the ELAVL1/SCD mRNA interaction

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机构: [1]Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, 410013 Changsha, Hunan, China [2]Postdoctoral Station of Basic Medicine, TheThird Xiangya Hospital of Central South University, 410013 Changsha, Hunan, China [3]Department of Pediatrics, The First Affiliated Hospital, University of South China, 421001Hengyang, Hunan, China [4]School of Basic Medical Science, Central South University, 410078 Changsha, Hunan, China [5]State Key Laboratory of Oncology in South China, SunYat‑Sen University Cancer Center, 510060 Guangzhou, Guangdong, China [6]Department of Gastrointestinal & Thyroid Surgery, The First Affiliated Hospital of GuangzhouUniversity of Traditional Chinese Medicine, 510405 Guangzhou, Guangdong, China [7]Department of Critical Care Medicine, The Second Xiangya Hospital of Central SouthUniversity, 410013 Changsha, Hunan, China
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Circular RNAs (circRNAs) are covalently closed noncoding RNA molecules that play multiple roles in tumorigenesis and metastasis. Ferroptosis is an iron-dependent, regulated form of cell death and has emerged as a promising target for cancer treatment. However, whether and how circRNAs regulate ferroptotic cell death in colorectal cancer (CRC) remains largely unknown. Three circRNA microarrays were used to screen differentially expressed circRNAs in CRC tissues. A series of functional experiments were conducted to investigate the effects of circRNA on CRC cell proliferation, migration and ferroptosis. We found that hsa_circ_0058495 (circRHBDD1), a novel circRNA, was significantly upregulated in colorectal cancer tissues and cells. The expression levels of circRHBDD1 in serum samples were strongly associated with the advancement of CRC. Silencing of circRHBDD1 remarkably suppressed the proliferation and migration of CRC cells in vitro. Moreover, the depletion of circRHBDD1 notably increased ferroptotic cell death and enhanced RSL3-induced ferroptosis in CRC cells. Mechanistically, circRHBDD1 upregulated the expression of stearoyl-CoA desaturase (SCD), a ferroptosis suppressor mediating lipid remodelling, by enhancing the ELAVL1/SCD mRNA interaction. Finally, circRHBDD1 knockdown repressed the tumorigenesis and ferroptosis of CRC cells in vivo. In conclusion, circRHBDD1 facilitates tumour progression and obstructs ferroptosis in CRC by regulating SCD expression in an ELAVL1-dependent manner.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 2 区 生物工程与应用微生物 3 区 遗传学 3 区 医学:研究与实验 4 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 3 区 遗传学 3 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2022]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY
最新[2024]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

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第一作者机构: [1]Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, 410013 Changsha, Hunan, China [2]Postdoctoral Station of Basic Medicine, TheThird Xiangya Hospital of Central South University, 410013 Changsha, Hunan, China
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通讯机构: [1]Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, 410013 Changsha, Hunan, China [7]Department of Critical Care Medicine, The Second Xiangya Hospital of Central SouthUniversity, 410013 Changsha, Hunan, China
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