Department of Thoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
Department of Medical Genetics, College of Basic Medical Science, Third Military Medical University, Chongqing, China; Department of Respiratory Medicine, The General Hospital of PLA Rocket Force, Beijing, China.
Biochem Biophys Res Commun. 2019 May 21;513(1):73-80. doi: 10.1016/j.bbrc.2019.03.012. Epub 2019 Mar 29.
An increasing number of long noncoding RNAs (lncRNAs) have been discovered, and dysregulation of lncRNAs plays critical roles in tumorigenesis and tumor progression. In this study, we identified a novel lncRNA LINC01980, located in both the cytoplasm and nucleus, which was significantly upregulated in esophageal squamous cell carcinoma (ESCC) tissues through microarray profiling. Further analysis revealed that LINC01980 overexpression was positively correlated with deeper invasion of cancer, positive lymph node metastasis, and advanced TNM stage. Additionally, high LINC01980 expression in ESCC tissues was associated with poor prognosis. In vitro and in vivo experiments demonstrated that LINC01980 promoted ESCC growth. EdU incorporation assay implied that LINC01980 accelerated ESCC proliferation. Flow cytometry analysis showed that knockdown of LINC01980 induced cell cycle arrest and increased apoptosis. Microarray analysis indicated that LINC01980 upregulated the expression of growth arrest and DNA damage inducible 45 alpha (GADD45A). Further experiments demonstrated that GADD45A promoted ESCC cell growth, indicating that GADD45A may be a downstream target of LINC01980. In conclusion, this study identified LINC01980 as a novel potential oncogene in ESCC, which can be a promising biomarker for prognosis and therapeutic targeting in ESCC.
越来越多的长非编码 RNA(lncRNA)被发现,lncRNA 的失调在肿瘤发生和肿瘤进展中起着关键作用。在这项研究中,我们通过微阵列分析鉴定了一种位于细胞质和细胞核中的新型 lncRNA LINC01980,其在食管鳞状细胞癌(ESCC)组织中显著上调。进一步分析表明,LINC01980 的过表达与癌症浸润更深、淋巴结阳性转移和晚期 TNM 分期呈正相关。此外,ESCC 组织中 LINC01980 的高表达与预后不良相关。体外和体内实验表明,LINC01980 促进了 ESCC 的生长。EdU 掺入实验表明 LINC01980 加速了 ESCC 的增殖。流式细胞术分析表明,LINC01980 的敲低诱导细胞周期停滞并增加细胞凋亡。微阵列分析表明 LINC01980 上调了生长停滞和 DNA 损伤诱导 45α(GADD45A)的表达。进一步的实验表明,GADD45A 促进了 ESCC 细胞的生长,表明 GADD45A 可能是 LINC01980 的下游靶标。总之,本研究鉴定了 LINC01980 作为 ESCC 中的一种新型潜在致癌基因,它可能是 ESCC 预后和治疗靶向的有前途的生物标志物。