+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      miR-21-5p Inhibits Ferroptosis in Hepatocellular Carcinoma Cells by Regulating the AKT/mTOR Signaling Pathway through MELK


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          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.


          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.


          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 Fe 2+ 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.


          In summary, this study demonstrates that miR-21-5p inhibits the ferroptosis of HCC cells by regulating the AKT/mTOR signaling pathway through MELK.

          Related collections

          Most cited references56

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer statistics, 2018

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
            • Record: found
            • Abstract: found
            • Article: not found

            Hepatocellular carcinoma

            Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed.
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Ferroptosis: past, present and future

              Ferroptosis is a new type of cell death that was discovered in recent years and is usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process; the occurrence of ferroptosis is iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. This paper systematically summarizes the latest progress in ferroptosis research, with a focus on providing references for further understanding of its pathogenesis and for proposing new targets for the treatment of related diseases.

                Author and article information

                J Immunol Res
                J Immunol Res
                Journal of Immunology Research
                24 March 2023
                : 2023
                : 8929525
                1First People's Hospital of Kunming City, Kunming 650032, Yunnan, China
                2The Calmette Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
                Author notes

                Academic Editor: Eirini Rigopoulou

                Author information
                Copyright © 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.

                : 26 October 2022
                : 8 January 2023
                : 10 February 2023
                Funded by: National Natural Science Foundation of China
                Award ID: 82060436
                Funded by: Reserve Talent Project for Young and Middle-aged Academic Technology Leaders in Yunnan Province
                Award ID: 202205AC160089
                Funded by: Yunnan Province Medical Discipline Leader Project
                Award ID: D-2018032
                Funded by: Kunming Medical University
                Award ID: J11301854
                Funded by: Spring City Plan: the High-level Talent Promotion and Training Project of Kunming
                Award ID: 2022SCP002
                Funded by: Yunnan Kunming Chen Ceshi Expert Workstation
                Award ID: YSZ-JFZZ-2020025
                Funded by: Yunnan Xuxiao Expert Workstation
                Award ID: 202205AF150064
                Research Article


                Comment on this article