Department of General Surgery, Huzhou Central Hospital, Huzhou, China.
Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Cancer Med. 2017 Oct;6(10):2321-2330. doi: 10.1002/cam4.1168. Epub 2017 Aug 31.
The colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide, but the pathogenesis of CRC remains not well-known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lncRNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome-wide comprehensive analysis of lncRNAs profiling and clinical relevance to identify novel lncRNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were annotated and analyzed to find differentially expressed lncRNAs in CRC. Analysis of these datasets revealed that hundreds of lncRNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lncRNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lncRNAs expression levels are significantly associated with CRC patients overall and recurrence-free survivals, such as H19, LEF1-AS1, and RP11-296E3.2. Furthermore, we identified one liver metastasis-associated lncRNA termed LUCAT1 in CRC by analyzing lncRNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss-of-function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lncRNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC.
结直肠癌(CRC)是全球癌症相关死亡的主要原因之一,但 CRC 的发病机制仍不清楚。越来越多的研究强调了长非编码 RNA(lncRNA)在肿瘤发生和癌细胞转移中的关键作用,然而,lncRNA 的表达模式、生物学功能及其在 CRC 中的作用机制仍不清楚。在这项研究中,我们对 lncRNA 谱进行了全基因组综合分析,并与临床相关性进行了分析,以确定用于 CRC 进一步研究的新型 lncRNA。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获得的 RNA 测序和微阵列数据被注释和分析,以发现 CRC 中差异表达的 lncRNA。对这些数据集的分析表明,与正常组织相比,CRC 组织中数百个 lncRNA 的表达失调。通过基因组变异分析,我们发现这些 lncRNA 失调中的一些与拷贝数扩增或缺失有关。此外,许多 lncRNA 的表达水平与 CRC 患者的总生存期和无复发生存期显著相关,如 H19、LEF1-AS1 和 RP11-296E3.2。此外,我们通过分析有肝转移和无肝转移的 CRC 患者组织中的 lncRNA 表达谱,鉴定出一个与 CRC 肝转移相关的 lncRNA,称为 LUCAT1。最后,通过功能丧失实验确定,敲低 LUCAT1 可损害 CRC 细胞的侵袭能力。总之,异常表达的 lncRNA 可能在 CRC 的发展和肝转移中发挥关键作用,我们的研究结果可能为 CRC 新型生物标志物的鉴定提供有用的资源。