Pan Yutian, Fang Yuan, Xie Mengyan, Liu Yu, Yu Tao, Wu Xi, Xu Tongpeng, Ma Pei, Shu Yongqian
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.
Department of the Orthopaedics, RWTH Aachen University Clinic, Pauwelsstrasse 30, 52074 Aachen, Germany.
Mol Ther Nucleic Acids. 2020 Oct 4;22:766-778. doi: 10.1016/j.omtn.2020.09.038. eCollection 2020 Dec 4.
Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are dysregulated in diverse tumors and take a pivotal role in modulating biological processes. In our study, a decreased expression level of LINC00675 in gastric cancer (GC) was first determined by data from The Cancer Genome Atlas (TCGA) and was identified using specimens from GC patients. Then, and functional experiments elaborated that LINC00675 could suppress cell proliferation and migration in GC. Multiple differentially expressed genes (DEGs) in LINC00675-overexpressing cells were identified through RNA sequencing analysis. An RNA-binding protein immunoprecipitation (RIP) assay was conducted to reveal that LINC00675 competitively bound with lysine-specific demethylase 1 (LSD1). A coimmunoprecipitation (coIP) assay indicated that LINC00675 overexpression may strengthen the binding of LSD1 and H3K4me2, whereas the chromatin immunoprecipitation (ChIP) assay results verified lower expression of H3K4me2 at the sprouty homolog 4 (SPRY4) promoter region. Together, our research identified that LINC00675 was remarkably downregulated in GC tissues and cells relative to nontumor tissues and cells. LINC00675 could repress GC tumorigenesis and metastasis via competitively binding with LSD1 and intensifying the binding of LSD1 and its target H3K4me2. Importantly, this contributed to attenuated binding of H3K4me2 at the promoter region of oncogene SPRY4 and suppressed SPRY4 transcription, thus suppressing GC cell proliferation and migration.
越来越多的证据表明，长链非编码RNA（lncRNA）在多种肿瘤中表达失调，并在调节生物学过程中起关键作用。在我们的研究中，首先通过癌症基因组图谱（TCGA）的数据确定了胃癌（GC）中LINC00675的表达水平降低，并使用GC患者的标本进行了鉴定。然后，功能实验表明LINC00675可以抑制GC中的细胞增殖和迁移。通过RNA测序分析鉴定了LINC00675过表达细胞中的多个差异表达基因（DEG）。进行了RNA结合蛋白免疫沉淀（RIP）试验，以揭示LINC00675与赖氨酸特异性去甲基化酶1（LSD1）竞争性结合。免疫共沉淀（coIP）试验表明，LINC00675的过表达可能会增强LSD1与H3K4me2的结合，而染色质免疫沉淀（ChIP）试验结果证实了在Sprouty同源物4（SPRY4）启动子区域H3K4me2的表达较低。总之，我们的研究发现，相对于非肿瘤组织和细胞，LINC00675在GC组织和细胞中显著下调。LINC00675可以通过与LSD1竞争性结合并增强LSD1与其靶标H3K4me2的结合来抑制GC的肿瘤发生和转移。重要的是，这有助于减弱癌基因SPRY4启动子区域H3K4me2的结合并抑制SPRY4转录，从而抑制GC细胞的增殖和迁移。
