Circular RNA circ_0000372 contributes to the proliferation, migration and invasion of colorectal cancer by elevating IL6 expression via sponging miR-495.

Circular RNAs are thought to play a vital function in the progression of various cancers, including colorectal cancer (CRC). However, the biological function and mechanism of circ_0000372 in CRC are still not clear. The expression of circ_0000372 and microRNA (miR)-495 was examined by quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit 8 and colony formation assays. Further, cell migration and invasion were assessed using transwell assay. Additionally, western blot analysis was used to detect the expression of proteins associated with proliferation, metastasis, Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signaling pathway and interleukin 6 (IL6). Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-495 and circ_0000372 or IL6. Furthermore, the effect of circ_0000372 on CRC tumor growth in vivo was explored using the mice xenograft models. Circ_0000372 was markedly upregulated in CRC, and its high expression was associated with the poor prognosis of CRC patients. Silenced circ_0000372 was able to suppress CRC cell proliferation, migration and invasion in vitro and CRC tumor growth in vivo. Bioinformatics prediction and experimental verification proposed that circ_0000372 could sponge miR-495, and miR-495 could target IL6. Besides, the JAK2/STAT3 signaling pathway activation could be regulated by circ_0000372, miR-495 and IL6. Rescue assay results confirmed that the inhibition effect of circ_0000372 knockdown on the proliferation and metastasis of CRC could be reversed by miR-495 inhibitor or IL6 overexpression. In short, we concluded that circ_0000372 promoted CRC progression by regulating the miR-495/IL6 axis, suggesting that circ_0000372 could be used as a new prognostic biomarker and therapeutic target for CRC.

Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients.

Mucosal associated invariant T (MAIT) cells are important for immune defense against infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8(+) MAIT cells were significantly reduced while tumor infiltrating MAIT cells were increased, especially in patients with advanced CRC. The serum CEA levels were positively correlated with the percentages of tumor infiltrating MAIT cells in CRC patients, but negatively correlated with the percentages of circulating MAIT in advanced CRC patients. Activated circulating MAIT cells from CRC patients produced lower IFN-γ, but higher IL-17. Furthermore, higher levels of Vα7.2-Jα33, IFN-γ and IL-17A were expressed in the CRC tissues. Co-culture of activated MAIT cells with HCT116 cells enhanced IL-17 expression and induced HCT116 cell cycle arrest at G2/M phase in a contact- and dose-dependent manner, which was abrogated by treatment with anti-MR1. Therefore, MAIT cells preferably infiltrate into the solid tumor in CRC patients and may participate in the immune surveillance of CRC.

A Higher Frequency of CD14+ CD169+ Monocytes/Macrophages in Patients with Colorectal Cancer.

OBJECTIVE: Monocytes and macrophages can infiltrate into tumor microenvironment and regulate the progression of tumors. This study aimed at determining the frequency of different subsets of circulating monocytes and tumor infiltrating macrophages (TIMs) in patients with colorectal cancer (CRC). METHODS: The frequency of different subsets of circulating monocytes was characterized in 46 CRC patients and 22 healthy controls (HC) by flow cytometry. The frequency of different subsets of macrophages was analyzed in TIMs from 30 tumor tissues and in lamina propria mononuclear cells (LPMCs) from 12 non-tumor tissues. The concentrations of plasma cytokines and carcinoembryonic antigen (CEA) were determined. The potential association of these measures with the values of clinical parameters was analyzed. RESULTS: In comparison with that in the HC, the percentages of circulating CD14+ CD169+, CD14+ CD169+ CD163+ and CD14+ CD169+ CD206+ monocytes and TIMs CD14+ CD169+ as well as IL-10+ CD14+ CD169+, but not IL-12+ CD14+ CD169+ macrophages were significantly increased, accompanied by higher levels of plasma IL-10 in the CRC patients. The percentages of CD14+ CD169+ circulating monocytes and TIM macrophages were associated with the stage of disease and correlated positively with the levels of plasma IL-10 and CEA in CRC patients. CONCLUSION: Our data suggest that an increase in the frequency of CD14+ CD169+ cells may be associated with the development and progression of CRC and is concomitant rise of both, pro-tumor (M2-like, IL-10 producing) and anti-tumor (M1-like, IL-12 producing) monocytes and infiltrating macrophages. The frequency of CD14+ CD169+ circulating monocytes and infiltrating macrophages may serve as a biomarker for evaluating the pathogenic degrees of CRC.