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Cell viability, proliferation, migration, and invasion were assessed with CCK-8, EdU, colony formation, and Transwell assays, alongside RT-qPCR, western blotting, dual-luciferase reporter, and coimmunoprecipitation. Results show miR-21-5p and MELK promote malignant phenotypes and alter ferroptosis regulators (GPX4, GSH, FTH1, xCT, HO-1), while erastin partly counteracts miR-21-5p 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[https://doi.org/10.1155/2023/8929525](https://doi.org/10.1155/2023/8929525)  \nResearch Article  \nmiR-21-5p Inhibits Ferroptosis in Hepatocellular Carcinoma Cells by Regulating the AKT/mTOR Signaling Pathway through MELK  \nZongqiang Hu , 1,2 Laibang Li, 1,2 Ma Li, 1,2 Xibing Zhang, 1,2 Yu Zhang, 1,2  \nJianghua Ran , 1,2 and Li Li 1,2  \n1First People ’s Hospital of Kunming City, Kunming 650032, Yunnan, China  \n2 The Calmette Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China  \nCorrespondence should be addressed to Jianghua Ran; [ranjianghua@kmmu.edu.cn and Li](ranjianghua@kmmu.edu.cn and Li) Li; [lili6@kmmu.edu.cn](lili6@kmmu.edu.cn)  \nReceived 26 October 2022; Revised 8 January 2023; Accepted 10 February 2023; Published 24 March 2023  \nAcademic Editor: Eirini Rigopoulou  \nCopyright © 2023 Zongqiang Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nBackground. Hepatocellular carcinoma (HCC) is one of the most prevalent cancers, and its incidence rate is increasing worldwide. At present, there is no ideal treatment for HCC. In recent years, molecular-targeted therapy has shown significant therapeutic benefits for patients. Ferroptosis is a modality of regulated cell death, and previous studies have found that inducing ferroptosis in liver cancer cells can inhibit the progression of liver cancer. The aim of this study is to investigate the regulatory mechanism of miR-21-5p in regulating ferroptosis in HCC cells. Methods. CCK-8 was used to measure cell viability, EdU and colony formation were used to measure cell proliferation, and Transwell assays were used to measure cell migration and invasion. RT-qPCR was used to detect the level of miR-21-5p, Western blotting was used to detect the protein expression level, a dual-luciferase reporter gene assay was used to determine the targeting relationship between miR-21-5p and MELK, and coimmunoprecipitation was used to determine the interaction between MELK and AKT. Results. Overexpression of miR-21-5p and MELK facilitated the viability, proliferation, colony formation, invasion, and migration of HCC cells. Downregulation of miR-21-5p suppressed the level of MELK and the progression of HCC. MELK regulated the AKT/mTOR signaling pathway, causing changes in the levels of GPX4, GSH, FTH1, xCT, heme oxygenase 1(HO-1), reactive oxygen species, and Fe2+ to regulate the ferroptosis of hepatoma cells. Erastin, an inducer of ferroptosis, attenuated the repressive influence of miR-21-5p on ferroptosis in HCC cells. Conclusion. In summary, this study demonstrates that miR-21-5p inhibits the ferroptosis ofHCC cells by regulating the AKT/mTOR signaling pathway through MELK.  \n1. Introduction  \nHepatocellular carcinoma (HCC) is one of the most prevalent cancers, and its morbidity is increasing worldwide. At present, there is no ideal treatment for HCC, and the prognosis of HCC patients is very poor. Many researchers are trying to improve the treatment effect by changing the treatment strategy [1] . Ferroptosis is a modality of regulated cell death characterized by an iron-dependent accumulation of lipid hydrogen peroxide to cell lethal levels. Since most of the body’s excess iron is stored in the liver, the liver is crucial in maintaining iron homeostasis. Proteins that control the cell cycle have been reported to be regulated by iron levels [2] . Therefore, cancer cells show an increased demand for iron to promote their proliferation, and this iron dependence makes  \ncancer cells more susceptible to ferroptosis, leading to cancer cell death [3–5] . In addition, the tumor inhibitor p53 is a transcription factor that is activated in response to cellular stress, and its expression is also regulated by altered iron metaboli","cbCair81n9uTfdgw","https://ap.wps.com/l/cbCair81n9uTfdgw","pdf",6123916,"English","# Background and Rationale\n## Ferroptosis and HCC\n## MicroRNAs and miR-21-5p\n## MELK and AKT/mTOR Signaling\n# Aim and Methods\n## Study Aim\n## Experimental Methods\n# Results and Conclusion","[{\"question\":\"What is the primary purpose of this study on miR-21-5p and HCC?\",\"answer\":\"To investigate the regulatory mechanism by which miR-21-5p affects ferroptosis in hepatocellular carcinoma cells.\"},{\"question\":\"How were miR-21-5p and MELK related to HCC cell behavior in the results?\",\"answer\":\"Overexpression of miR-21-5p and MELK facilitated viability, proliferation, colony formation, invasion, and migration, while downregulation suppressed MELK levels and HCC progression.\"},{\"question\":\"Through which pathway does MELK influence ferroptosis in hepatoma cells?\",\"answer\":\"MELK regulates the AKT/mTOR signaling pathway, leading to changes in ferroptosis-associated factors such as GPX4, GSH, FTH1, xCT, and HO-1.\"}]","miR-21-5p Inhibits Ferroptosis in Hepatocellular Carcinoma Cells by Regulating the AKT/mTOR Signaling Pathway through MELK | PDF",1790560293]