Journal
MOLECULAR CANCER
Volume 21, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12943-022-01630-9
Keywords
Prostate cancer; Epithelial mesenchymal transformation; CircSMARCC1; CC-chemokine ligand 20; Tumor-associated macrophage
Categories
Funding
- National Natural Science Foundation of China [81972394]
- China Postdoctoral Science Foundation [2019 M662865]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515010066, 2022A1515010437]
- Distinguished Young Talents in Higher Education Foundation of Guangdong Province [2019KQNCX115]
- Science and Technology Plan Project of Guangzhou [202102010150]
- Achievement Cultivation and Clinical Transformation Application Cultivation projects of the First Affiliated Hospital of Guangzhou Medical University [ZH201908]
- President's Foundation of the Third Affiliated Hospital of Southern Medical University [YM2021010]
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This study reveals that circSMARCC1 upregulates the secretion of chemokine CCL20 by sponging miR-1322, which mediates the interaction between tumor cells and TAMs, promoting the progression of PCa.
Background 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. Methods 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. Results 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. Conclusions 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.
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