Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
J Cell Physiol. 2020 Oct;235(10):6592-6604. doi: 10.1002/jcp.29529. Epub 2020 Feb 17.
An increasing number of studies have explored the relationship of long noncoding RNAs (lncRNAs) with cervical cancer, yet the role of LINC00511 in cervical cancer still remains elusive. The current dissertation was intended to explore the effect of LINC00511 on cervical cancer development by regulating phospholipase D1 (PLD1) expression through transcription factor retinoic X receptor alpha (RXRA). Differentially expressed lncRNA and messenger RNA related to cervical cancer were screened by microarray-based expression profiling. Cervical cancer and paracancerous tissues were harvested to determine the LINC00511 expression using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The relationship among LINC00511, PLD1 promoter activity, and RXRA were determined via RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Proliferation, autophagy, and apoptosis of cervical cancer cells were detected with a series of experiments. Tumor xenograft in nude mice was employed to determine the influence of LINC00511 and PLD1 on tumor formation and growth of cervical cancer in vivo. LINC00511 might influence the occurrence of cervical cancer by upregulating PLD1 expression via recruiting transcription factor RXRA. LINC00511 and PLD1 expressions were remarkably high in cervical cancer tissues and cells. LINC00511 combined with RXRA, and overexpression of LINC00511 in cervical cancer cells elevated PLD1 expression. Si-LINC00511, si-RXRA or si-PLD1 triggered repression of proliferation and promotion of autophagy and apoptosis of cervical cancer cells. In vivo experiment, si-LINC00511, or si-PLD1 inhibited the tumorigenic ability of nude mice. Collectively, this study suggests that LINC00511 acts as an oncogenic lncRNA in cervical cancer via the promotion of transcription factor RXRA-regulated PLD1.
越来越多的研究探讨了长链非编码 RNA（lncRNA）与宫颈癌的关系，但 LINC00511 在宫颈癌中的作用仍不清楚。本论文旨在通过转录因子视黄酸 X 受体α（RXRA）调节磷脂酶 D1（PLD1）表达来探讨 LINC00511 对宫颈癌发展的影响。通过基于微阵列的表达谱筛选与宫颈癌相关的差异表达 lncRNA 和信使 RNA。使用逆转录定量聚合酶链反应和 Western blot 分析从宫颈癌和癌旁组织中测定 LINC00511 的表达。通过 RNA 免疫沉淀、染色质免疫沉淀和双荧光素酶报告基因测定来确定 LINC00511、PLD1 启动子活性和 RXRA 之间的关系。通过一系列实验检测宫颈癌细胞的增殖、自噬和凋亡。在裸鼠中进行肿瘤异种移植实验，以确定 LINC00511 和 PLD1 对体内宫颈癌肿瘤形成和生长的影响。LINC00511 可能通过募集转录因子 RXRA 上调 PLD1 表达来影响宫颈癌的发生。LINC00511 和 PLD1 在宫颈癌组织和细胞中表达明显升高。LINC00511 与 RXRA 结合，宫颈癌细胞中 LINC00511 的过表达可提高 PLD1 的表达。si-LINC00511、si-RXRA 或 si-PLD1 可抑制宫颈癌细胞的增殖并促进自噬和凋亡。体内实验中，si-LINC00511 或 si-PLD1 抑制了裸鼠的致瘤能力。总之，这项研究表明，LINC00511 通过促进转录因子 RXRA 调节的 PLD1 的表达，在宫颈癌中发挥致癌 lncRNA 的作用。
