Abstract

Colorectal cancer (CRC) is one of the most common human malignancies. An increasing body of evidence has revealed the important roles long noncoding RNA (lncRNA) plays in the growth dynamics of CRC cells. In this study, we aimed to define the role of LINC00337 in the malignant phenotypes, especially angiogenesis, of CRC and clarify the underlying molecular basis. Bioinformatic analyses identified promoter region methylation of CNN1 in CRC, which was further validated by BSP and MSP assays. Loss- and gain- of function approaches were used to determine the roles of CNN1 and LINC00337 in vitro and in vivo. MTT-based method, Transwell migration/invasion assays, and tube formation assay were adopted to evaluate the cancer cell proliferation, migration/invasion, and proangiogenetic potency respectively in vitro. The tumor growth, microvascular density (MVD) and markers of proliferation (Ki67) and angiogenesis (VEGF) were quantified in nude mice xenografted with CRC cells. It was found that CNN1 downregulation and LINC00337 overexpression occurred in CRC tissues and cells. Besides, the CNN1 promoter region was hypermethylated in CRC. CNN1 overexpression or LINC00337 knockdown restricted CRC cell proliferation, migration/invasion, and proangiogenetic potency in vitro, which was substantiated by the in vivo experiments evidenced by facilitated tumor growth and MVD as well as elevated Ki67 and VEGF. Furthermore, our mechanistic evidence revealed that LINC00337 recruited DNMT1 to the promoter region of CNN1 and restricted the transcription of CNN1. Taken together, this study indicates that LINC00337 facilitates the tumorigenesis and angiogenesis in CRC via recruiting DNMT1 to inhibit the expression of CNN1.