Circular RNAs (circRNAs) function as tumour promoters or suppressors in bladder cancer (BLCA) by regulating genes involved in macrophage recruitment and polarization. However, the underlying mechanisms are largely unknown. The aim of this study was to determine the biological role of circLOC729852 in BLCA. CircLOC729852 was upregulated in BLCA tissues and correlated with increased proliferation, migration and epithelial mesenchymal transition (EMT) of BCLA cells. MiR‐769‐5p was identified as a target for circLOC729852, which can upregulate IL‐10 expression by directly binding to and suppressing miR‐769‐5p. Furthermore, our results indicated that the circLOC729852/miR‐769‐5p/IL‐10 axis modulates autophagy signalling in BLCA cells and promotes the recruitment and M2 polarization of TAMs by activating the JAK2/STAT3 signalling pathway. In addition, circLOC729852 also promoted the growth of BLCA xenografts and M2 macrophage infiltration in vivo. Thus, circLOC729852 functions as an oncogene in BLCA by inducing secretion of IL‐10 by the M2 TAMs, which then facilitates tumour cell growth and migration. Taken together, circLOC729852 is a potential diagnostic biomarker and therapeutic target for BLCA.

中文翻译：

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CircRNA LOC729852 通过 miR-769-5p/IL-10 轴调节巨噬细胞极化和募集促进膀胱癌进展

环状 RNA (circRNA) 通过调节参与巨噬细胞募集和极化的基因，充当膀胱癌 (BLCA) 的肿瘤启动子或抑制子。然而，其根本机制在很大程度上尚不清楚。本研究的目的是确定 circLOC729852 在 BLCA 中的生物学作用。 CircLOC729852 在 BLCA 组织中表达上调，并与 BCLA 细胞的增殖、迁移和上皮间质转化 (EMT) 增加相关。 miR-769-5p 被确定为 circLOC729852 的靶标，它可以通过直接结合并抑制 miR-769-5p 来上调 IL-10 表达。此外，我们的结果表明，circLOC729852/miR-769-5p/IL-10轴调节BLCA细胞中的自噬信号传导，并通过激活JAK2/STAT3信号通路促进TAM的募集和M2极化。此外，circLOC729852还促进体内BLCA异种移植物的生长和M2巨噬细胞浸润。因此，circLOC729852 通过诱导 M2 TAM 分泌 IL-10，充当 BLCA 中的癌基因，从而促进肿瘤细胞的生长和迁移。综上所述，circLOC729852 是 BLCA 的潜在诊断生物标志物和治疗靶点。