Department of Gastrointestinal Colorectal Surgery, the Third Hospital of Jilin University, Jilin University, Changchun, Jilin, 130033, China.
Department of Ultrasound, the Third Hospital of Jilin University, Jilin University, Changchun, Jilin, 130033, China.
Pathol Oncol Res. 2020 Oct;26(4):2659-2667. doi: 10.1007/s12253-020-00862-8. Epub 2020 Jul 11.
Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RT-qPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cell-based assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling.
结直肠癌仍然是全球预后较差的最常见癌症类型之一。近年来,大量研究表明 lncRNAs 在结直肠癌进展中起关键作用。本研究旨在探讨 FGF14-AS2 在结直肠癌发生发展中的作用。在 TCGA 数据集,发现 FGF14-AS2 是一个显著下调的 lncRNA。通过 RT-qPCR,我们证实了收集的结直肠癌样本中 FGF14-AS2 的下调。转染含有全长 FGF14-AS2 的质粒可抑制结直肠癌细胞的增殖,并诱导细胞凋亡。此外,FGF14-AS2 的过表达可使细胞中 MAPK/ERK 信号失活。生物信息学分析和随后的细胞实验表明,FGF14-AS2 可作为结直肠癌中的致癌 miRNA-1288-3p 的海绵。RAS/ERK 通路的调节因子 RERG 被预测并验证为 miR-1288 的靶基因。通过下调 miR-1288,FGF14-AS2 可提高结直肠癌细胞中 RERG 的表达。挽救实验表明,FGF14-AS2 通过调节 RERG 来控制结直肠癌细胞的增殖和凋亡。综上所述,本研究表明 FGF14-AS2 通过下调 miR-1288-3p 和失活 Ras/ERK 信号通路来调控结直肠癌的发生发展。