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.

结直肠癌 (CRC) 是最常见的人类恶性肿瘤之一。越来越多的证据揭示了长链非编码 RNA (lncRNA) 在 CRC 细胞生长动力学中的重要作用。在这项研究中，我们旨在确定 LINC00337 在 CRC 的恶性表型，尤其是血管生成中的作用，并阐明潜在的分子基础。生物信息学分析确定了 CRC 中 CNN1 的启动子区域甲基化，这通过 BSP 和 MSP 测定得到了进一步验证。功能损失和获得方法用于确定 CNN1 和 LINC00337 在体外和体内的作用。采用基于 MTT 的方法、Transwell 迁移/侵袭试验和管形成试验分别评估体外癌细胞增殖、迁移/侵袭和促血管生成效力。肿瘤生长，在异种移植 CRC 细胞的裸鼠中量化微血管密度 (MVD) 和增殖标志物 (Ki67) 和血管生成 (VEGF)。发现 CNN1 下调和 LINC00337 过表达发生在 CRC 组织和细胞中。此外，CNN1 启动子区域在 CRC 中被高甲基化。CNN1 过表达或 LINC00337 敲低在体外限制了 CRC 细胞增殖、迁移/侵袭和促血管生成效力，体内实验证实了这一点，促进了肿瘤生长和 MVD 以及 Ki67 和 VEGF 升高。此外，我们的机制证据显示 LINC00337 将 DNMT1 募集到 CNN1 的启动子区域并限制 CNN1 的转录。综合起来，