Objective: We aimed to construct the ferritin autophagy regulatory network and illustrate its mechanism in ferroptosis, TME immunity and malignant phenotypes of ovarian cancer. Methods: First, we used Western blot assays and immunohistochemistry to detect the pathway expression in ovarian cancer samples (C-MYC, NCOA4). Then, we performed RIP and FISH analysis to verify the targeted binding of these factors after which we constructed ovarian cancer cell models and detected pathway regulator expression (NCOA4). Co-localization and Western blot assays were used to detect ferritin autophagy in different experimental groups. We selected corresponding kits to assess ROS contents in ovarian cancer cells. MMP was measured using flow cytometry and mitochondrial morphology was observed through TEM. Then, we chose Clone, EdU and Transwell to evaluate the proliferation and invasion abilities of ovarian cancer cells. We used Western blot assays to measure the DAMP content in ovarian cancer cell supernatants. Finally, we constructed tumor bearing models to study the effect of the C-MYC pathway on ovarian cancer tumorigenesis and TME immune infiltration in in vivo conditions. Results: Through pathway expression detection, we confirmed that C-MYC was obviously up-regulated and NCOA4 was obviously down-regulated in ovarian cancer samples, while their expression levels were closely related to the malignancy degree of ovarian cancer. RIP, FISH and cell model detection revealed that C-MYC could down-regulate NCOA4 expression through directly targeted binding with its mRNA. Ferritin autophagy and ferroptosis detection showed that C-MYC could inhibit ferroptosis through NCOA4-mediated ferritin autophagy, thus reducing ROS and inhibiting mitophagy in ovarian cancer cells. Cell function tests showed that C-MYC could promote the proliferation and invasion of ovarian cancer cells through the NCOA4 axis. The Western blot assay revealed that C-MYC could reduce HMGB1 release in ovarian cancer cells through the NCOA4 axis. In vivo experiments showed that C-MYC could promote tumorigenesis and immune evasion in ovarian cancer cells through inhibiting HMGB1 release induced by NCOA4-mediated ferroptosis. Conclusion: According to these results, we concluded that C-MYC could down-regulate NCOA4 expression through directly targeted binding, thus inhibiting ferroptosis and promoting malignant phenotype/immune evasion in ovarian cancer cells through inhibiting ferritin autophagy.

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Background: TMZ resistance plays a critical role in the treatment of glioma, our research try to explore how circRNAs affect the chemosensitivity of glioma cells. Methods: In this study, we proceeded gene sequencing, and selected circRNAs specifically expressed in TMZ resistant cells and use them as target genes for subsequent studies; by knocking out the target gene we clarify its effect on TMZ resistant glioma proliferation, invasion, migration and cell apoptosis; through tumor-burdened animals we explore the effect of target gene in vivo environment. Results: In our research we revealed that circ-GLIS3 was significantly upregulated in TMZ resistant glioma cells. Functionally, knocking down circ-GLIS3 could inhibit proliferation, invasion, and migration abilities of TMZ resistant glioma cells; moreover, the downregulation of circ-GLIS3 could induce cell cycle arrest and apoptosis, while miR-548m inhibition and MED31 mRNA could reverse this progress. In vivo condition, the silencing of circ-GLIS3 could induce cell apoptosis and suppressed tumor growth. Mechanistically, circ-GLIS3 positively upregulated MED31 expression by sponging miR-548m. Conclusions: All these research findings demonstrate that circ-GLIS3 accelerates TMZ resistant glioma progression through miR-548m/MED31 axis.

ObjectiveIn our research we try to explore whether glioma stem cell containing circRNAs signal pathway could regulate glioma malignant progression and elaborate its possible mechanism.MethodsIn this study, we used biological information analysis to build an RNA regulatory network and then proceeded RT-PCR to screen target RNAs, after that we clarified the targeting relationship between circRNA-miRNA-mRNA through double luciferase gene assay, RNA pull down experiment, PCR and Western Blot. Finally we adopted RNA transfection to identify its impact on glioma cell proliferation, invasion, migration, apoptosis and cell cycle.Resultscirc-ASB3 was significantly up-regulated in glioma stem cells compared with glioma cells. The circ-ASB3/miR-543/Twist1 axis was discovered to be a possible regulatory pathway in glioma, circ-ASB3 could adsorb and targeted bind to miR-543, down-regulate miR-543 expression, thus release its targeted inhibition to Twist1. Circ-ASB3 was shown to increase glioma cell proliferation, invasion, and migration in vitro via miR-543/Twist1 axis. Meanwhile glioma cell apoptosis could be inhibited, and cell cycle arrest could be induced through this signaling pathway.Conclusioncirc-ASB3 could enhance glioma malignancy via miR-543/Twist1 axis, resulting in the discovery of new biomarkers and possible therapeutic targets for these patients.