简介：环状 RNA (circRNA) 已被确定为癌症发展和进展的重要贡献者。本研究的目的是检测circRNA circ_BBS9在肺腺癌（LUAD）中的表达和临床意义，以及其潜在的作用模式。通过利用微阵列检测Circ_BBS9在肺腺癌组织和细胞系中的表达分析、实时定量聚合酶链反应 (qRT-PCR) 和蛋白质印迹分析。在本研究中，我们评估了 circ_BBS9 对 LUAD 细胞增殖的影响，及其对铁死亡和肿瘤形成的影响。为了分析这些影响，我们采用了 CCK-8 检测和铁死亡检测。通过利用 RNA Pull-down 和质谱技术，鉴定了与 Circ_BBS9 相互作用的蛋白质。利用生物信息学研究建立了包含 circ_BBS9、miR-7150 和 IFIT3 的假定调控网络。研究还包括检查 IFIT3 表达与免疫细胞侵袭之间的相关性。Circ_BBS9 在 LUAD 组织和细胞系中显着下调。 circ_BBS9 低表达与不良预后相关。功能实验表明，circ_BBS9过表达可抑制LUAD细胞增殖并在体外促进铁死亡，在体内抑制肿瘤生长。从机制上讲，circ_BBS9被发现直接与IFIT3相互作用，并通过充当miR-7150的海绵来调节其表达。此外，IFIT3 表达与 LUAD 中的免疫浸润呈正相关。Circ_BBS9 已被确定为肺腺癌 (LUAD) 中的肿瘤抑制因子，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 直接相互作用以及与 miR-7150 竞争性结合来调节铁死亡和免疫微环境。上述研究结果为 LUAD 的病理生理学提供了新的视角，并强调 circ_BBS9 作为治疗干预的潜在有价值的靶点。版权所有 © 2024 Peng、Liang、Li、Yang、Fang、Chen 和guan。

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.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.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.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.Copyright © 2024 Peng, Liang, Li, Yang, Fang, Chen and Guan.