Guo Caixia, Shi Hongmei, Shang Yuli, Zhang Yafei, Cui Jiajia, Yu Hongtao
Department of Respiratory Medicine, Henan Provincial Chest Hospital, No.1, Weiwu Road, Zhengzhou, 450000 Henan Province China.
Cancer Cell Int. 2020 Jun 26;20:275. doi: 10.1186/s12935-020-01332-6. eCollection 2020.
LncRNAs are key regulators in cancer. The current study explored the role of lncRNA LINC00261 (LINC00261) in lung cancer (LC).
Expression of LINC00261 in LC tissues and cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Pearson's Chi square test and Kaplan-Meier analysis were performed to evaluate the correlations between LINC00261 expression and clinical characteristics, and overall survival time. A549 and SPC-A1 cells were transfected with LINC00261 overexpression plasmid, cell viability, cell number, and apoptosis were detected by CCK-8 assay, colony formation, and flow cytometry. Moreover, wound-healing and transwell assay were performed to detect cell metastasis and invasion. Expressions of proteins related to cell proliferation and metastasis were determined by Western blot. Xenograft was constructed, and tumor size and weight were measured and the effects of LINC00261 overexpression on tumor growth were detected. Bioinformatics analysis, dual-luciferase reporter assay, qRT-PCR, correlation analysis, and functional rescue experiments were conducted on clinical cases and LC cells to explore the molecular mechanism of LINC00261 in LC.
In LC, LINC00261 expression was down-regulated, and was associated with more advanced TNM stage, metastasis and a shorter survival time. LINC00261 overexpression inhibited the growth and metastasis of LC cells in vitro and tumor growth in vivo. Furthermore, miR-1269a directly interacted with LINC00261 and FOXO1. The expressions of miR-1269a and FOXO1 were dysregulated by LINC00261 in LC. Additionally, miR-1269a promoted the progression of LC through targeting FOXO1.
Down-regulation of LINC00261 expression has a prognostic value in LC, and overexpression LINC00261 inhibits LC progression via targeting miR-1269a/FOXO1 axis.
长链非编码RNA（lncRNAs）是癌症中的关键调节因子。本研究探讨了lncRNA LINC00261（LINC00261）在肺癌（LC）中的作用。
采用定量实时聚合酶链反应（qRT-PCR）检测LINC00261在LC组织和细胞中的表达。采用Pearson卡方检验和Kaplan-Meier分析评估LINC00261表达与临床特征及总生存时间之间的相关性。用LINC00261过表达质粒转染A549和SPC-A1细胞，通过CCK-8法、集落形成实验和流式细胞术检测细胞活力、细胞数量和凋亡情况。此外，进行伤口愈合实验和Transwell实验检测细胞转移和侵袭能力。通过蛋白质印迹法检测与细胞增殖和转移相关的蛋白质表达。构建异种移植模型，测量肿瘤大小和重量，检测LINC00261过表达对肿瘤生长的影响。对临床病例和LC细胞进行生物信息学分析、双荧光素酶报告基因实验、qRT-PCR、相关性分析和功能挽救实验，以探讨LINC00261在LC中的分子机制。
在LC中，LINC00261表达下调，且与更晚期的TNM分期、转移及较短的生存时间相关。LINC00261过表达在体外抑制LC细胞的生长和转移，在体内抑制肿瘤生长。此外，miR-1269a直接与LINC00261和FOXO1相互作用。在LC中，LINC00261使miR-1269a和FOXO1的表达失调。此外，miR-1269a通过靶向FOXO1促进LC进展。
LINC00261表达下调在LC中具有预后价值，过表达LINC00261通过靶向miR-1269a/FOXO1轴抑制LC进展。
