Department of Anorectal Surgery, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, People's Republic of China.
Department of General Surgery, Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangyin, 214400, People's Republic of China.
Dig Dis Sci. 2020 Feb;65(2):442-456. doi: 10.1007/s10620-019-05801-5. Epub 2019 Sep 20.
Colorectal cancer (CRC) is one of the most prevalent cancers and a common cause of cancer-related death. Long noncoding RNAs have been reported to play an essential role in the development of CRC.
This study aimed to investigate the possible function of LINC00460 in CRC.
Initially, microarray-based gene expression profiling of CRC was employed to identify differentially expressed genes. Next, the expression of LINC00460 was examined and the cell line presenting with the highest LINC00460 expression was selected for subsequent experimentation. Then, the interaction among LINC00460, ERG, and WWC2 was identified. The effect of LINC00460 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT)-related factors as well as tumorigenicity of transfected cells was examined with gain- and loss-of-function experiments.
LINC00460 was robustly induced while WWC2 was poorly expressed in CRC. In addition, LINC00460 could down-regulate WWC2 through interaction with ERG, which led to promoted invasion, migration, and EMT of CRC cells in addition to tumor growth in vivo. Besides, down-regulation of LINC00460 exerted inhibitory effect on these biological activities.
Taken together, the key findings of the current study provided evidence suggesting that silencing of LINC00460 could potentially suppress EMT of CRC cells by increasing WWC2 via ERG, and highlighting that knockdown of LINC00460 could serve as a therapeutic target for CRC treatment.
结直肠癌（CRC）是最常见的癌症之一，也是癌症相关死亡的常见原因。长链非编码 RNA 已被报道在 CRC 的发展中发挥重要作用。
本研究旨在探讨 LINC00460 在 CRC 中的可能作用。
首先，采用基于微阵列的 CRC 基因表达谱分析来鉴定差异表达基因。接下来，检测 LINC00460 的表达，并选择表达 LINC00460 最高的细胞系进行后续实验。然后，鉴定 LINC00460、ERG 和 WWC2 之间的相互作用。通过增益和缺失功能实验，研究 LINC00460 对转染细胞增殖、迁移、侵袭和上皮-间充质转化（EMT）相关因子以及致瘤性的影响。
LINC00460 在 CRC 中强烈诱导，而 WWC2 表达水平较低。此外，LINC00460 可以通过与 ERG 相互作用下调 WWC2，导致 CRC 细胞的侵袭、迁移和 EMT 增强，以及体内肿瘤生长。此外，下调 LINC00460 对这些生物学活性具有抑制作用。
综上所述，本研究的主要发现提供了证据表明，通过 ERG 增加 WWC2，沉默 LINC00460 可能抑制 CRC 细胞的 EMT，并且敲低 LINC00460 可能成为 CRC 治疗的治疗靶点。
