Wu Qiong, Wei Jue, Zhao Chen, Xiang Shihao, Shi Min, Wang Yugang
Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Aging (Albany NY). 2020 Nov 7;15(2):583-594. doi: 10.18632/aging.103790.
Long non-coding RNA EPIC1 (Lnc-EPIC1) binds MYC protein, which is essential for MYC function and expression of MYC target genes. The current study tested its expression and potential functions in human colon cancer cells. We show that Lnc-EPIC1 expression is elevated in human colon cancer tissues and primary human colon cancer cells. Whereas its expression is relatively low in normal colon tissues and colon epithelial cells. In the primary human colon cancer cells, Lnc-EPIC1 siRNA largely inhibited cancer cell growth, proliferation, migration and invasion. Further, Lnc-EPIC1 silencing induced significant apoptosis activation in colon cancer cells. Conversely, ectopic overexpression of Lnc-EPIC1 augmented colon cancer cell growth, proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down results confirmed that Lnc-EPIC1 directly binds MYC protein in colon cancer cells. MYC target proteins, including cyclin A, cyclin D and CDK9, were downregulated with Lnc-EPIC1 silencing, but upregulated after Lnc-EPIC1 overexpression in colon cancer cells. Further Lnc-EPIC1 silencing or overexpression failed to alter functions of MYC-knockout colon cancer cells. Collectively, overexpressed Lnc-EPIC1 is important for the progression of human colon cancer cells.
长链非编码RNA EPIC1（Lnc-EPIC1）与MYC蛋白结合，这对MYC功能及MYC靶基因的表达至关重要。本研究检测了其在人结肠癌细胞中的表达及潜在功能。我们发现，Lnc-EPIC1在人结肠癌组织和原代人结肠癌细胞中表达升高，而在正常结肠组织和结肠上皮细胞中表达相对较低。在原代人结肠癌细胞中，Lnc-EPIC1 siRNA在很大程度上抑制了癌细胞的生长、增殖、迁移和侵袭。此外，Lnc-EPIC1沉默诱导结肠癌细胞中显著的凋亡激活。相反，Lnc-EPIC1的异位过表达增强了结肠癌细胞的生长、增殖、迁移和侵袭。RNA免疫沉淀和RNA下拉实验结果证实，Lnc-EPIC1在结肠癌细胞中直接与MYC蛋白结合。包括细胞周期蛋白A、细胞周期蛋白D和CDK9在内的MYC靶蛋白，在Lnc-EPIC1沉默后下调，但在结肠癌细胞中Lnc-EPIC1过表达后上调。此外，Lnc-EPIC1沉默或过表达未能改变MYC基因敲除的结肠癌细胞的功能。总体而言，过表达的Lnc-EPIC1对人结肠癌细胞的进展很重要。
