Department of General Surgery.
Department of Oncology, Taizhou People's Hospital, Taizhou Clinical Medical College of Nanjing Medical University, Medical School of Nantong University, Taizhou, Jiangsu.
Anticancer Drugs. 2021 Jan 1;32(1):66-73. doi: 10.1097/CAD.0000000000000975.
A growing number of evidence has revealed that aberrantly expressed long noncoding RNAs (lncRNAs) are involved in the development of a variety of malignancies, including colorectal cancer (CRC). However, the clinical relevance of most lncRNAs and their potential biological functions in CRC remains poorly understood. The aim of this study was to identify the key lncRNAs related to patient prognosis as well as their biological function and underlying mechanism in CRC. Therefore, five independent datasets containing CRC and normal tissue RNA sequencing, microarray data and the corresponding clinical data from The Cancer Genome Atlas and Gene Expression Omnibus were screened. Hundreds of significantly differentially expressed lncRNAs in CRC were determined, and Kaplan-Meier analyses revealed that some of these lncRNAs were related to the overall survival and progression-free survival of patients with CRC, such as RP11-108K3.2, FOXD3-AS1, H19 and AP001469.9. Among these dysregulated lncRNAs, LINC02163 and FEZF1-AS1 were significantly upregulated in CRC tissues, suggesting that they may have oncogenic roles in CRC. Furthermore, loss of function assays revealed that downregulation of LINC02163 and FEZF1-AS1 impaired CRC cell proliferation. In addition, RNA Immunoprecipitation and Chromatin Immunoprecipitation assays determined that FEZF1-AS1 regulates CRC cell growth via interacting with LSD1 and repressing KLF2 expression. Collectively, hundreds of dysregulated lncRNAs and their associated biological roles identified in this study may provide potentially useful biomarkers and therapeutic targets for CRC.
越来越多的证据表明,异常表达的长非编码 RNA(lncRNA)参与了多种恶性肿瘤的发展,包括结直肠癌(CRC)。然而,大多数 lncRNA 的临床相关性及其在 CRC 中的潜在生物学功能仍知之甚少。本研究旨在鉴定与患者预后相关的关键 lncRNA 及其在 CRC 中的生物学功能和潜在机制。因此,筛选了包含 CRC 和正常组织 RNA 测序、微阵列数据以及来自癌症基因组图谱和基因表达综合数据库的相应临床数据的五个独立数据集。确定了数百个在 CRC 中差异表达的显著 lncRNA,Kaplan-Meier 分析显示,这些 lncRNA 中的一些与 CRC 患者的总生存期和无进展生存期相关,例如 RP11-108K3.2、FOXD3-AS1、H19 和 AP001469.9。在这些失调的 lncRNA 中,LINC02163 和 FEZF1-AS1 在 CRC 组织中明显上调,表明它们可能在 CRC 中具有致癌作用。此外,功能丧失实验表明,下调 LINC02163 和 FEZF1-AS1 会损害 CRC 细胞的增殖。此外,RNA 免疫沉淀和染色质免疫沉淀实验确定,FEZF1-AS1 通过与 LSD1 相互作用并抑制 KLF2 的表达来调节 CRC 细胞的生长。总之,本研究中鉴定的数百个失调 lncRNA 及其相关生物学作用可能为 CRC 提供潜在有用的生物标志物和治疗靶点。