Gao Hongyan, Song Xiaodi, Kang Ting, Yan Baohong, Feng Li, Gao Li, Ai Liang, Liu Xiaoni, Yu Jie, Li Huiqi
Department of Gastroenterology, The First Affiliated Hospital of Xi'an Medical University.
Department of Pharmacy, Xi'an Central Hospital, Xi'an.
Onco Targets Ther. 2017 Jan 5;10:205-216. doi: 10.2147/OTT.S116178. eCollection 2017.
Colorectal neoplasia differentially expressed () is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis. Overexpression of promoted the migration and invasion potency of colorectal cancer cells. Furthermore, we found that conferred chemoresistance in colorectal cancer cells. Knockdown of with OXA treatment decreased cell viability and promoted DNA damage and cell apoptosis, while the overexpression of with OXA treatment reduced DNA damage and cell apoptosis. Further in-depth mechanistic studies revealed that functioned as a competing endogenous RNA for miR-136, led to the de-repression of its endogenous target, E2F transcription factor 1 (E2F1). Overall, our findings demonstrate that functions as a competing endogenous RNA to promote metastasis and OXA resistance by sponging miR-136 in colorectal cancer.
结直肠癌差异表达基因()是一种新发现的基因,被认为是一种长链非编码RNA(lncRNA),在结直肠癌和许多其他实体瘤中高度上调,但其在转移和奥沙利铂(OXA)耐药方面的功能尚不清楚。在我们的研究中,我们证实了在结直肠癌患者的原发标本和结直肠癌细胞系中均上调。敲低表达可抑制结直肠癌细胞的迁移和侵袭能力,而对细胞凋亡无影响。过表达可促进结直肠癌细胞的迁移和侵袭能力。此外,我们发现可赋予结直肠癌细胞化疗耐药性。用OXA处理敲低可降低细胞活力,促进DNA损伤和细胞凋亡,而用OXA处理过表达可减少DNA损伤和细胞凋亡。进一步深入的机制研究表明,可作为miR-136的竞争性内源性RNA,导致其内源靶标E2F转录因子1(E2F1)的去抑制。总体而言,我们的研究结果表明,在结直肠癌中作为竞争性内源性RNA通过海绵吸附miR-136促进转移和OXA耐药。