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Our results suggest that miR-590-5p inhibits intestinal inflammation in mouse colon and tumourigenesis of colorectal cancer cells by inhibiting YAP. The miR-590-5p/YAP axis may be an important novel mechanism in the pathogenesis of CD and colorectal cancer.

Background/Aims: ADAMTSs (A disintegrin and metalloprotease domains with thrombospondins motifs) are a family of extracellular proteases that have been related to both oncogenic and tumor-suppressive functions. The aim of the present study was to investigate: 1) the mutation, copy-number alterations, and expression profile of ADAMTSs in colorectal cancer and 2) whether ADAMTSs participate in colorectal cancer (CRC) progression and invasion. Methods: The mutation, copy-number alterations, and expression profile of ADAMTSs in CRC were analyzed in the TCGA cohort using cBioportal. ADAMTS4 expression in tumor tissues and cell lines were determined by immunostaining and real-time quantitative PCR. The role of ADAMTS-4 in CRC progression and the underlying mechanisms were studied by using short hairpin RNA-mediated knockdown of ADAMTS4. The effects of ADAMTS4 in cell proliferation and invasion were determined by clone formation assay and transwell migration assay, respectively. Macrophages were depleted by liposomal clodronate in immune-competent BALB/c mice and tumor growth was analyzed. Results: ADAMTS4 was differentially expressed in CRC and predicted a poor prognosis. Elevated ADAMTS4 expression was closely associated with larger tumor size, enhanced TNM stage, and a poor clinical outcome in patients with CRC. ADAMTS4 knockdown had no inhibitory implications on cell proliferation and invasion in vitro, but significantly attenuated tumor growth in vivo. Mechanistically, we revealed that ADAMTS4 was associated macrophages infiltration and polarization in the tumor microenvironment of CRC. Macrophage depletion largely abolished the promotive effect of ADAMTS4 on tumor growth in the immune competent BALB/c mice. Conclusion: ADAMTS4 seemed to be a promising prognostic indicator in CRC. The novel link between ADAMTS4 and macrophages mirrors the potential regulatory roles of ADAMTSs in the inflammatory microenvironment of cancers.

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MiRNAs, as oncogenes or as anti-oncogenes, play critically regulated roles in the initiation and progression of colorectal cancer at posttranscriptional level. However, the underlying functions of miR-27b in colorectal cancer remain largely unexplored. Here, we demonstrated miR-27b is significantly down-regulated in colorectal cancer tissues, and decreased miR-27b expression was closely associated with shorter overall survival of patients with colorectal cancer. By gain- and loss-of-function studies, we showed miR-27b remarkably suppressed cell proliferation and invasion of colorectal cancer. Furthermore, luciferase reporter assay identified Rab3D was the direct functional target of miR-27b. And Rab3D partly reversed the suppression of cell proliferation and invasion caused by miR-27b mimics. Finally, the animal experiment showed miR-27b plays a crucial role on colorectal cancer progression by targeting Rab3D. Taken together, our study implied miR-27b inhibits cell growth and invasion by targeting Rab3D, and miR-27b is a potential biomarker for prognosis and therapeutic target in colorectal cancer.