Xiao Yuhang, Tang Jinming, Yang Desong, Zhang Baihua, Wu Jie, Wu Zhining, Liao Qianjin, Wang Hui, Wang Wenxiang, Su Min
Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Department of Pharmacy, Xiangya Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Biomark Res. 2022 Aug 16;10(1):60. doi: 10.1186/s40364-022-00408-x.
Esophageal squamous cell carcinoma (ESCC) represents a major malignancy with poor clinical outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of multiple cancers. However, how lncRNAs are involved in ESCC is currently undefined.
LIPH-4 levels in ESCC tissue specimens and cells were assessed by qRT-PCR. The biological function of LIPH-4 was examined in cell and animal studies, applying CCK-8, EdU, colony formation and flow cytometry assays as well as xenograft model experiments. The underlying mechanisms of action of LIPH-4 were explored through bioinformatics, luciferase reporter assay, RNA-immunoprecipitation assay and immunoblot.
We identified a novel lncRNA, LIPH-4, which showed elevated amounts in ESCC tissues and positive correlations with increased tumor size and poor prognosis in ESCC patients. Functional studies showed that LIPH-4 promoted the growth, mediated cell cycle progression and inhibited apoptosis in ESCC cells in vitro, and promoted tumor growth in mice. In terms of mechanism, LIPH-4 could bind to miR-216b and act as a competing endogenous RNA (ceRNA) to induce the expression of miR-216's target gene IGF2BP2. LIPH-4 played an oncogenic role in ESCC through the miR-216b/IGF2BP2 axis.
This study suggested that LIPH-4 functions as a novel oncogenic lncRNA by acting as a ceRNA for miR-216b to regulate IGF2BP2, indicating LIPH-4 likely constitutes a prognostic biomarker and therapeutic target in ESCC.
食管鳞状细胞癌(ESCC)是一种临床预后较差的主要恶性肿瘤。已知长链非编码RNA(lncRNAs)可调节多种癌症的发生和发展。然而,lncRNAs如何参与ESCC目前尚不清楚。
通过qRT-PCR评估ESCC组织标本和细胞中LIPH-4的水平。在细胞和动物研究中,应用CCK-8、EdU、集落形成和流式细胞术分析以及异种移植模型实验来检测LIPH-4的生物学功能。通过生物信息学、荧光素酶报告基因检测、RNA免疫沉淀检测和免疫印迹来探索LIPH-4的潜在作用机制。
我们鉴定出一种新型lncRNA,LIPH-4,其在ESCC组织中的含量升高,并且与ESCC患者肿瘤大小增加和预后不良呈正相关。功能研究表明,LIPH-4在体外促进ESCC细胞的生长、介导细胞周期进程并抑制细胞凋亡,在小鼠中促进肿瘤生长。在机制方面,LIPH-4可以与miR-216b结合并作为竞争性内源性RNA(ceRNA)来诱导miR-216靶基因IGF2BP2的表达。LIPH-4通过miR-216b/IGF2BP2轴在ESCC中发挥致癌作用。
本研究表明,LIPH-4作为miR-216b的ceRNA调节IGF2BP2,发挥新型致癌lncRNA的功能,表明LIPH-4可能构成ESCC的预后生物标志物和治疗靶点。