Journal Article

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling

Yu, Yu-zhong, Li, Kang-jin, Xie, Tao, Fu, Du-jiang, Zhao, Shan-Chao, Feng, Ning-Han, Zhai, Baoqian, Wang, Chong, Wu, Jiacheng, Song, Xian-Lu, Li, Zhi-min, Lv, Dao-jun

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Phosphatidylinositol 3-kinase / AKT protein / Antibodies / Biomarkers / Biomedical and Life Sciences / Biomedicine / Biotin / Cancer Research / Cancer therapies / Carcinogenesis / CC-chemokine ligand 20 / CCL20 protein / CCR6 protein / CD163 antigen / Cell adhesion & migration / Cell culture / Cell growth / Cell proliferation / Chemokines / CircSMARCC1 / Development and progression / Epithelial mesenchymal transformation / Experiments / Fluorescence in situ hybridization / Hospitals / Infiltration / Macrophages / Medical prognosis / Medical research / Mesenchyme / Metastases / Metastasis / Oncology / Prostate cancer / Proteins / Reagents / RNA / RNA sequencing / Signal transduction / Stem cells / Tumor cells / Tumor microenvironment / Tumor-associated macrophage / Tumors