LncRNA LINC01671/YY1 positive feedback loop induced EMT modulates CCL2 secretion in colorectal cancer to attract M2-like TAM infiltration

Background: Epithelial-mesenchymal transition (EMT) is involved in the interaction between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME), which intimately affects tumorigenicity and metastasis. However, the potential mechanisms of EMT and the understanding of how EMT-programmed cancer cells affect TAMs recruitment and polarization remain further investigation. Methods The expression of LINC01671, miR-141-3p, miR-186-5p, and YY1 in CRC tissues and cells were detected by RT-qPCR. Functions of LINC01671 on cancer cell proliferation, migration, invasion and EMT were examined by a series of in vitro assays. The underlying mechanism of LINC01671 was investigated by bioinformatics analysis, RNA pull-down, luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation assays. A co-culture assay in vitro was used to detect the effect of LINC01671 on macrophage recruitment and polarization in TME. A xenograft mouse model was performed to explore the role of LINC01671 on tumorigenicity and TAM polarization. Results LncRNA LINC01671 was significantly overexpressed in colorectal cancer (CRC) tissues, and high LINC01671 level was positively correlated with poor prognosis in CRC patients. Elevated LINC01671 promoted CRC cells proliferation, migration, invasion and EMT in vitro as well as tumor growth and metastasis in vivo. Mechanistically, LINC01671 served as a sponge for miR-141-3p and miR-186-5p to facilitate YY1 expression, which in turn transcriptionally activated LINC01671 expression. Moreover, LINC01671/YY1 modulated CCL2 secretion during CRC cells EMT and subsequently favored TAMs infiltration and M2-like polarization in TME. Conclusion Our data demonstrate that LINC01671, identified as an oncogene, may play a crucial role in regulating YY1-mediated cancer cell EMT, thereby affecting CCL2-related M2-like TAM recruitment in CRC.