Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Urology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510500, China.
Mol Cancer. 2022 Sep 1;21(1):173. doi: 10.1186/s12943-022-01630-9.
Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain.
Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1.
CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68/CD163/CD206 TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression.
CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.
环状 RNA（circRNAs）可调节肿瘤相关巨噬细胞（TAMs）的浸润，促进各种类型癌症的发生和发展。然而，circRNAs 在调节前列腺癌（PCa）中巨噬细胞的作用仍不确定。
通过 RNA 测序鉴定 PCa 中差异表达的 circRNAs。采用荧光原位杂交和实时定量 PCR 鉴定和评估 circSMARCC1 的表达。通过一系列体外和体内实验研究 circSMARCC1 在 PCa 肿瘤增殖和转移中的致癌作用。最后，通过 Western blot、生物素标记的 RNA 下拉、荧光素酶测定、挽救实验以及与 TAMs 的共培养实验，揭示 circSMARCC1 的作用机制。
circSMARCC1 在 PCa 细胞、血浆和组织中显著上调。circSMARCC1 的过表达促进了体外和体内的肿瘤增殖和转移，而 circSMARCC1 的敲低则产生相反的效果。机制上，circSMARCC1 通过海绵吸附 miR-1322 调节趋化因子配体 20（CCL20）的表达，并激活参与增殖和上皮间质转化的 PI3K-Akt 信号通路。更重要的是，circSMARCC1 的高表达与肿瘤微环境中 CD68/CD163/CD206 TAMs 的定植呈正相关。此外，circSMARCC1 通过 CCL20-CCR6 轴促进巨噬细胞中 CD163 的表达，诱导 TAMs 的浸润和 M2 极化，从而导致 PCa 的进展。
circSMARCC1 通过海绵吸附 miR-1322 上调趋化因子 CCL20 的表达，通过靶向 CCL20/CCR6 信号通路参与肿瘤细胞与 TAMs 的相互作用，促进 PCa 的进展。
