Department of Pathology, Jinshan Branch of Shanghai Sixth People's Hospital, Shanghai, China.
Department of Automation, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2024 Jul 19;15:1344954. doi: 10.3389/fimmu.2024.1344954. eCollection 2024.
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 and suppressed tumor growth . 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.
介绍：环状 RNA（circRNAs）已被确定为癌症发生和发展的重要贡献者。本研究的目的是研究肺腺癌（LUAD）中 circRNA circ_BBS9 的表达及其临床意义，以及其潜在的作用方式。
通过使用微阵列分析、定量实时聚合酶链反应（qRT-PCR）和 Western blot 分析，检测 LUAD 组织和细胞系中 circ_BBS9 的表达。在本研究中，我们评估了 circ_BBS9 对 LUAD 细胞增殖的影响，以及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 测定和铁死亡测定。通过使用 RNA 下拉和质谱技术来鉴定与 Circ_BBS9 相互作用的蛋白质。通过生物信息学研究建立了包括 circ_BBS9、miR-7150 和 IFIT3 的假定调控网络。还检查了 IFIT3 表达与免疫细胞浸润之间的相关性。
Circ_BBS9 在 LUAD 组织和细胞系中表达显著下调。低 circ_BBS9 表达与不良预后相关。功能实验表明，circ_BBS9 过表达抑制 LUAD 细胞增殖并促进铁死亡，抑制肿瘤生长。机制上，circ_BBS9 被发现可直接与 IFIT3 相互作用，并通过作为 miR-7150 的海绵来调节其表达。此外，IFIT3 的表达与 LUAD 中的免疫浸润呈正相关。
Circ_BBS9 被鉴定为肺腺癌（LUAD）的肿瘤抑制因子，有望成为诊断生物标志物。潜在的作用机制涉及通过与 IFIT3 的直接相互作用和竞争性结合 miR-7150 来调节铁死亡和免疫微环境。上述发现为 LUAD 的病理生理学提供了新的视角，并强调 circ_BBS9 作为潜在有价值的治疗靶点的潜力。
