Recently, many studies revealed that long noncoding RNAs (lncRNAs) play important roles in cancers. To identify lncRNAs contributing to colorectal cancers, we screened lncRNAs through expression and survival analyses in datasets from The Cancer Genome Atlas (TCGA). The screen revealed that RP11-278A23.1 expression is significantly increased in colorectal cancer tissues compared with normal tissues and that high RP11-278A23.1 expression correlates with poor prognosis. The knockdown of RP11-278A23.1 inhibited the growth of and promoted apoptosis in colorectal cancer cells. Next, to comprehensively examine differentially expressed genes after RP11-278A23.1 knockdown, RNA sequencing was performed in HCT116 cells. The expression of p21, a p53 target gene, was significantly upregulated, and the expression of several p53 target proapoptotic genes was also altered. RP11-278A23.1 knockdown increased p53 expression at the translational level but not at the transcriptional level. Interestingly, RP11-278A23.1 knockdown also altered the expression of these proapoptotic genes in DLD1 cells with mutated p53 and in p53-knockout HCT116 cells. These results suggest that RP11-278A23.1 modifies the expression of these apoptosis-related genes in p53-dependent and p53-independent manners. In summary, lncRNA RP11-278A23.1 contributes to colorectal cancer progression by promoting cell growth and inhibiting apoptosis, suggesting that this lncRNA may be a useful therapeutic target.
近期多项研究表明，长链非编码RNA在癌症发生发展中发挥重要作用。为鉴定与结直肠癌相关的lncRNA，我们基于癌症基因组图谱数据库，通过表达谱分析与生存分析进行系统性筛选。结果显示，RP11-278A23.1在结直肠癌组织中的表达水平显著高于正常组织，且其高表达与不良预后密切相关。敲低RP11-278A23.1可抑制结直肠癌细胞增殖并促进其凋亡。进一步通过RNA测序技术全面分析HCT116细胞中RP11-278A23.1敲低后的差异表达基因，发现p53靶基因p21表达显著上调，多个促凋亡基因表达亦发生改变。RP11-278A23.1敲低能在翻译水平而非转录水平提升p53表达。值得注意的是，在p53突变型DLD1细胞及p53敲除型HCT116细胞中，RP11-278A23.1敲低同样能改变这些促凋亡基因的表达模式。这些结果表明RP11-278A23.1可通过p53依赖与非依赖双重途径调控凋亡相关基因表达。综上所述，lncRNA RP11-278A23.1通过促进细胞增殖与抑制凋亡参与结直肠癌进展，提示该分子可能成为潜在治疗靶点。
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