Xu Xiaomin, Mao Xinting, Liu Wenrong, Ming Yue, Zhang Tingting, Yang Yang, Gu-Ha A-Lai, Lin Yi-Dan, Peng Yong
Center for Molecular Oncology Frontiers Science Center for Disease-Related Molecular Network State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu China.
Department of Thoracic Surgery West China Hospital Sichuan University Chengdu China.
MedComm (2020). 2025 May 23;6(6):e70218. doi: 10.1002/mco2.70218. eCollection 2025 Jun.
Long noncoding RNAs (lncRNAs) play important roles in tumorigenesis, but their biological functions and mechanisms in esophageal squamous cell carcinoma (ESCC) remain poorly understood. In this study, we employed high-throughput sequencing and bioinformatics analyses to identify the differentially expressed lncRNAs between ESCC tumors and adjacent normal tissues, among which LINC02820 is significantly upregulated in ESCC. Rapid amplification of cDNA ends assays determined the transcription initiation and termination sites of LINC02820, confirming it as a novel transcript variant localized in both the nucleus and cytoplasm of ESCC cells. Functional studies demonstrated that LINC02820 promotes cell proliferation and migration in vitro and enhances tumor growth and metastasis in vivo. Mechanistically, LINC02820 interacts with Myosin-9 protein and prevent it from ubiquitination-mediated proteasomal degradation. Additionally, the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 binds to LINC02820 and increase its RNA stability in ESCC cells, thus upregulating LINC02820 expression. Therefore, these findings indicate LINC02820 as an oncogenic lncRNA in ESCC progression and suggest its potential as a therapeutic target.
长链非编码RNA（lncRNAs）在肿瘤发生过程中发挥重要作用，但其在食管鳞状细胞癌（ESCC）中的生物学功能和机制仍知之甚少。在本研究中，我们采用高通量测序和生物信息学分析来鉴定ESCC肿瘤组织与相邻正常组织之间差异表达的lncRNAs，其中LINC02820在ESCC中显著上调。cDNA末端快速扩增实验确定了LINC02820的转录起始和终止位点，证实其为一种定位于ESCC细胞核和细胞质中的新型转录变体。功能研究表明，LINC02820在体外促进细胞增殖和迁移，并在体内增强肿瘤生长和转移。机制上，LINC02820与肌球蛋白9蛋白相互作用，阻止其通过泛素化介导的蛋白酶体降解。此外，RNA结合蛋白胰岛素样生长因子2 mRNA结合蛋白2与LINC02820结合，并增加其在ESCC细胞中的RNA稳定性，从而上调LINC02820的表达。因此，这些发现表明LINC02820是ESCC进展过程中的一种致癌lncRNA，并提示其作为治疗靶点的潜力。
