Background Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms. Methods Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). Results It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. Conclusion Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.

Background: The anti-tumor effect of interleukin (IL)-36β-mediated activation of CD8 + T cells has been reported, but the molecular mechanism is largely undefined. Methods:The levels of IL-36β in pancreatic cancer were examined by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. We then examined the changes of CD8 + T cells and natural killer (NK) cells in the tumor by flow cytometry. The microRNA expression profiles were determined by microarray analysis. Results:The results revealed decreased levels of IL-36β in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8 + T and NK cell proliferation in the tumor microenvironment (TME). Moreover, IL-36β stimulated CD8 + T cells to synthesize high amounts of interferon-gamma (IFN-γ) and IL-2. Microarray analysis showed that IL-36β administration to human and mouse CD8 + T cells consistently downregulated the miRNA, let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8 + T cells, whereas its upregulation had the opposite effect. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p + CD8 + T cells.Conclusions: These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8 + T cells, as well as anti-tumor effects in CD8 + T cells by downregulating let-7c-5p.

Background: The anti-tumor effect of IL-36β mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined.Methods: IL-36β amounts in pancreatic cancer were examined by qRT-PCR and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. Then we examined the changes of CD8+ T cells and NK cells in the tumor flow-cytometrically. MicroRNA expression profiles were determined by microarray analysis.Results: The results revealed decreased IL-36β amounts in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment. Moreover, IL-36β stimulated CD8+ T cells to synthesize high amounts of IFN-γ and IL-2. Microarray analysis showed that IL-36β administration to human and mouse CD8+ T cells consistently downregulated the miRNA let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8+ T Cells, whereas its upregulation had the opposite effects. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p+ CD8+ T cells. Conclusion: These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8+ T cells, and IL-36β promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.

Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study investigated the role of a novel circular RNA (circCSPP1) in colon cancer and explored the possible underlying molecular mechanisms. Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer specimens and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, Transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. The overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas the silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression levels of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. Notably, circCSPP1 from SW620 cells was transferred to macrophages via exosomes and enhanced the colon cancer microenvironment. Taken together, the findings of the present study indicated that circCSPP1 may functions as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.