本研究重点研究了循环RNA（circRNAs）在肺腺癌（LUAD）发生中的功能和机制。通过qRT-PCR和蛋白质免疫印迹分析检测了基因和蛋白质水平。采用乙炔基-2'-脱氧尿苷（EdU）、集落形成、流式细胞术和Transwell试验进行了体外试验。采用小鼠异种移植模型进行了体内实验。通过RIP和双荧光素酶报告基因分析确认了let-7a-2-3p和circHSPB6或CCL2之间的结合。通过流式细胞术分析了肿瘤相关巨噬细胞（TAMs）的M2极化。LUAD组织和细胞表现出较高的circHSPB6表达，circHSPB6的沉默抑制了LUAD细胞在体外的增殖、迁移、侵袭，并诱导细胞凋亡，同时在体内抑制了肿瘤生长。在机制上，circHSPB6/let-7a-2-3p/CCL2形成一个反馈回路。circHSPB6可以通过吸引let-7a-2-3p来调控CCL2的表达。进一步的救助试验表明，circHSPB6沉默对LUAD细胞的影响可以通过抑制let-7a-2-3p或过表达CCL2来逆转。此外，circHSPB6通过CCL2促进了TAMs的M2极化和浸润。功能上，circHSPB6对A549和H1299细胞的沉默抑制了TAM M2极化，从而抑制了细胞增殖、迁移、侵袭和EMT进展，而这些效应又被CCL2的上调逆转。circHSPB6通过let-7a-2-3p/CCL2轴诱导TAM M2极化，从而促进LUAD细胞的增殖、迁移、侵袭和EMT进展。© 2023年，作者（们）在Springer Science+Business Media, LLC独家许可下，Springer Nature的一部分。

Circular RNAs (circRNAs) are reported to be involved in the tumorigenesis of lung adenocarcinoma (LUAD). Here, this study focused on studying the function and mechanism of circHSPB6 in LUAD progression. Levels of genes and proteins were tested using qRT-PCR and western blotting analyses. The 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and transwell assays were adopted for in vitro assays. In vivo assay was conducted using mouse xenograft models. The binding between let-7a-2-3p and circHSPB6 or CCL2 was validated using RIP and dual-luciferase reporter assays. The M2 polarization of tumor-associated macrophages (TAMs) was analyzed by flow cytometry. LUAD tissues and cells showed high circHSPB6 expression, knockdown of circHSPB6-suppressed LUAD cell proliferation, migration, invasion, and induced cell apoptosis in vitro, as well as hindered tumor growth in vivo. Mechanistically, circHSPB6/let-7a-2-3p/CCL2 forms a feedback loop. CircHSPB6 could regulate CCL2 expression via sponging let-7a-2-3p. Further rescue assays showed that the effects of circHSPB6 silencing on LUAD cells were reversed by let-7a-2-3p inhibition or CCL2 overexpression. Moreover, circHSPB6 promoted the M2 polarization and infiltration of TAMs by CCL2. Functionally, circHSPB6 knockdown in A549 and H1299 cells inhibited TAM M2 polarization and then suppressed cell proliferation, migration, invasion, and emergency medical technicians (EMT) progression, while these effects were reversed by CCL2 up-regulation CircHSPB6 induced TAM M2 polarization to promote LUAD cell proliferation, migration, invasion, and EMT progression through let-7a-2-3p/CCL2 axis.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.