LOXL1-AS1通过m6a依赖性调控TFRC抑制宫颈癌铁下垂

IF 2.2 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-09-19 DOI:10.1007/s10735-025-10603-3

Hongyou Wang, Jianbo Zhou, Jianfeng Zhang, Wenlei Yao, Haiyang Li, Kangjie Xu, Hui Cheng

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引用次数: 0

摘要

转铁蛋白受体（TFRC）对铁摄取至关重要，并可能调节铁凋亡，铁凋亡是一种与宫颈癌（CC）有关的铁依赖性细胞死亡形式。生物信息学分析（GEPIA， UALCAN， SRAMP, starBase）结合体外和体内实验。转染了靶向TFRC和LOXL1-AS1的shrna或过表达质粒。通过菌落形成、EdU染色和Ki-67免疫染色评估增殖。通过测量丙二醛（MDA）、脂质ROS、Fe2⁺和铁中毒相关蛋白来评估铁中毒。RNA pull-down、RIP和MeRIP检测用于探索m6a依赖性调控，放线菌素D检测用于评估mRNA稳定性。TFRC和LOXL1-AS1在CC中表达上调，并与不良预后相关。TFRC促进CC细胞增殖，抑制铁下垂。LOXL1-AS1通过m6a - igf2bp2依赖机制稳定TFRC mRNA，从而正向调节TFRC。救援实验证实，TFRC过表达逆转了LOXL1-AS1敲低的作用。在体内，LOXL1-AS1缺失抑制肿瘤生长并增强铁下垂。LOXL1-AS1通过m6A-IGF2BP2相互作用稳定TFRC mRNA，抑制铁下垂，促进CC进展。靶向LOXL1-AS1/IGF2BP2/TFRC轴可能为CC提供潜在的治疗策略。

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LOXL1-AS1 suppresses ferroptosis in cervical cancer through m6A-dependent regulation of TFRC

Transferrin receptor (TFRC) is essential for iron uptake and may regulate ferroptosis, a form of iron-dependent cell death implicated in cervical cancer (CC). Bioinformatic analyses (GEPIA, UALCAN, SRAMP, starBase) were combined with in vitro and in vivo experiments. CC cell lines were transfected with shRNAs or overexpression plasmids targeting TFRC and LOXL1-AS1. Proliferation was assessed by colony formation, EdU staining, and Ki-67 immunostaining. Ferroptosis was evaluated by measuring malondialdehyde (MDA), lipid ROS, Fe²⁺, and ferroptosis-related proteins. RNA pull-down, RIP, and MeRIP assays were used to explore m6A-dependent regulation, and actinomycin D assays assessed mRNA stability. TFRC and LOXL1-AS1 were upregulated in CC and associated with poor prognosis. TFRC promoted CC cell proliferation and inhibited ferroptosis. LOXL1-AS1 positively regulated TFRC by stabilizing its mRNA via an m6A-IGF2BP2-dependent mechanism. Rescue experiments confirmed that TFRC overexpression reversed the effects of LOXL1-AS1 knockdown. In vivo, LOXL1-AS1 depletion suppressed tumor growth and enhanced ferroptosis. LOXL1-AS1 promoted CC progression by stabilizing TFRC mRNA through m6A-IGF2BP2 interaction, suppressing ferroptosis. Targeting the LOXL1-AS1/IGF2BP2/TFRC axis may offer a potential therapeutic strategy for CC.

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.