关键词: IFIT3 circ_BBS9 circular ribonucleic acids (circRNAs) ferroptosis immune microenvironment lung adenocarcinoma (LUAD)

Mesh : Humans Tumor Microenvironment / immunology genetics RNA, Circular / genetics Adenocarcinoma of Lung / immunology genetics diagnosis Lung Neoplasms / immunology genetics diagnosis Biomarkers, Tumor / genetics Animals Mice Gene Expression Regulation, Neoplastic Ferroptosis / genetics immunology Cell Line, Tumor MicroRNAs / genetics Male Cell Proliferation Female Apoptosis Regulatory Proteins / genetics metabolism RNA-Binding Proteins / genetics metabolism Middle Aged Mice, Nude Intracellular Signaling Peptides and Proteins

来  源:   DOI:10.3389/fimmu.2024.1344954   PDF(Pubmed)

Abstract:
UNASSIGNED: Introduction: Circular RNAs (circRNAs) have been identified as significant contributors to the development and advancement of cancer. The objective of this study was to examine the expression and clinical implications of circRNA circ_BBS9 in lung adenocarcinoma (LUAD), as well as its potential modes of action.
UNASSIGNED: The expression of Circ_BBS9 was examined in tissues and cell lines of LUAD through the utilization of microarray profiling, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. In this study, we assessed the impact of circ_BBS9 on the proliferation of LUAD cells, as well as its influence on ferroptosis and tumor formation. To analyze these effects, we employed CCK-8 assays and ferroptosis assays. The identification of proteins that interact with Circ_BBS9 was achieved through the utilization of RNA pull-down and mass spectrometry techniques. A putative regulatory network comprising circ_BBS9, miR-7150, and IFIT3 was established using bioinformatics study. The investigation also encompassed the examination of the correlation between the expression of IFIT3 and the invasion of immune cells.
UNASSIGNED: Circ_BBS9 was significantly downregulated in LUAD tissues and cell lines. Low circ_BBS9 expression correlated with poor prognosis. Functional experiments showed that circ_BBS9 overexpression inhibited LUAD cell proliferation and promoted ferroptosis in vitro and suppressed tumor growth in vivo. Mechanistically, circ_BBS9 was found to directly interact with IFIT3 and regulate its expression by acting as a sponge for miR-7150. Additionally, IFIT3 expression correlated positively with immune infiltration in LUAD.
UNASSIGNED: Circ_BBS9 has been identified as a tumor suppressor in lung adenocarcinoma (LUAD) and holds promise as a diagnostic biomarker. The potential mechanism of action involves the modulation of ferroptosis and the immunological microenvironment through direct interaction with IFIT3 and competitive binding to miR-7150. The aforementioned findings offer new perspectives on the pathophysiology of LUAD and highlight circ_BBS9 as a potentially valuable target for therapeutic interventions.
摘要:
简介:环状RNA(circularRNAs)已被确定为癌症发展和进展的重要贡献者。这项研究的目的是检查circRNAcirc_BBS9在肺腺癌(LUAD)中的表达和临床意义,以及它潜在的行动模式。
通过利用微阵列分析在LUAD的组织和细胞系中检查Circ_BBS9的表达,定量实时聚合酶链反应(qRT-PCR),和蛋白质印迹分析。在这项研究中,我们评估了circ_BBS9对LUAD细胞增殖的影响,以及它对铁死亡和肿瘤形成的影响。为了分析这些影响,我们采用CCK-8测定和铁凋亡测定。通过利用RNA下拉和质谱技术实现与Circ_BBS9相互作用的蛋白质的鉴定。使用生物信息学研究建立了包含circ_BBS9、miR-7150和IFIT3的推定调控网络。该研究还包括检查IFIT3的表达与免疫细胞侵袭之间的相关性。
Circ_BBS9在LUAD组织和细胞系中显著下调。低circ_BBS9表达与不良预后相关。功能实验表明,circ_BBS9过表达在体外抑制LUAD细胞增殖,促进铁凋亡,在体内抑制肿瘤生长。机械上,发现circ_BBS9直接与IFIT3相互作用,并通过充当miR-7150的海绵来调节其表达。此外,LUAD中IFIT3的表达与免疫浸润呈正相关。
Circ_BBS9已被确定为肺腺癌(LUAD)的肿瘤抑制因子,并有望作为诊断生物标志物。潜在的作用机制涉及通过与IFIT3的直接相互作用和与miR-7150的竞争性结合来调节铁凋亡和免疫微环境。上述发现为LUAD的病理生理学提供了新的观点,并强调了circ_BBS9作为治疗干预的潜在有价值的目标。
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