Colorectal cancer (CRC) threatens the health of patients with high mortality, which lacks sensitive biomarkers for diagnosis to improve total survival. The lncRNA NBR2 is reported to be downregulated in CRC and suppresses the proliferation of CRC cells. However, the underlying mechanisms remain unclear. The present study aimed to explore the regulatory function of the lncRNA NBR2 on tumor-associated macrophage (TAM) polarization and its consequent anti-tumor effect. Two CRC cell lines were used in this study. We found that the lncRNA NBR2, TNF-α, and HLA-DR were downregulated, and Arg-1, CD163, CD206, and IL-4 were upregulated in CRC tumors. M1 polarization was activated and M2 polarization was suppressed in NBR2-overexpressed macrophages, accompanied by increased production of inflammatory factors, decreased proliferation, and inhibited migration ability in the co-culture system of HCT-116 cells (SW480 cells) and NBR2overexpressed macrophages. The promoted proliferation and migration were observed in the coculture system of HCT-116 cells (SW480 cells) and NBR2-knockdown macrophages. The tumor growth of both HCT-116 cells and SW480 cells in the xenograft model was suppressed by coplanting NBR2-overexpressed macrophages and was facilitated by the co-planting of NBR2knockdown macrophages. The release of inflammatory factors was induced, M1 polarization was facilitated, and M2 polarization was suppressed in tumor tissues in the NBR2-overexpressed group, which were all reversed in the NBR2-knockdown group. Therefore, the lncRNA NBR2 suppressed the progression of colorectal cancer in vitro and in vivo by regulating TAM polarization.
Circular RNAs (circRNAs) are a class of noncoding RNAs that are widely expressed in cancer tissues and play a pro-or anticancer role in modulating cancer progression. This work is aimed to probe the biological role of circ_0000317 in colorectal cancer (CRC) and its underlying mechanism. Circ_0000317 was selected from the circRNA microarray datasets (GSE121895). Quantitative real-time polymerase chain reaction was utilized to examine circ_0000317, microRNA (miR)-520g, and homeobox D10 (HOXD10) mRNA expression in CRC. Cell Counting Kit-8 and Transwell experiments were conducted to examine the effects of circ_0000317 on proliferation, migration, and invasion of CRC cells. Bioinformatic analysis and dual-luciferase reporter gene experiments were implemented to predict and validate the targeting relationship between circ_0000317 and miR-520g, miR-520g, and HOXD10. Western blot was employed to examine HOXD10 expression at protein level in CRC cells. Circ_0000317 and HOXD10 mRNA expression were unveiled to be down-modulated and miR-520g expression was upmodulated in CRC. Functionally, circ_0000317 overexpression repressed CRC cell proliferation, migration, and invasion. Mechanistically, miR-520g was a direct target of circ_0000317 and miR-520g specifically modulated HOXD10 expression. Furthermore, miR-520g mimics partially counteracted the suppressing effect of circ_0000317 on malignant phenotype of CRC cells. Circ_0000317 represses CRC progression by targeting miR-520g and modulating HOXD10 expression. Hence, circ_0000317 may be a promising diagnostic biomarker and a therapeutic target for CRC.
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