Shu Yang, Zhang He, Li Jinqiu, Shan Yanhong
Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, China.
Department of Gynecology, The First Hospital of Jilin University, Changchun, China.
Front Oncol. 2021 Jan 28;10:541410. doi: 10.3389/fonc.2020.541410. eCollection 2020.
Ovarian cancer represents one of the most frequent gynecological cancers and is significant cause of death for women around the world. Long non-coding RNAs (lncRNAs) are recognized as critical governors of gene expression during carcinogenesis, but their effects on the occurrence and development of ovarian cancer require further investigation. In this report, we characterized LINC00494 as a novel oncogenic lncRNA in ovarian cancer.
Bioinformatics analysis predicted potential interactions among LINC00494, NFκB1, and FBXO32 in ovarian cancer, which were tested by dual-luciferase reporter assay, RNA pull-down, RIP, and ChIP assay. Cancer cells were transfected with relevant treated plasmids, followed by scratch and Transwell assays. The treated cells were injected into nude mice to establish a xenograft model for testing effects of LINC00494 and its target gene .
LINC00494 and NFκB1 were highly expressed whereas FBXO32 had low expression in ovarian cancer cells and tissues. LINC00494 was found to bind NFκB1 and increase its activity, while NFκB1 was enriched at the FBXO32 promoter region, where it acted to reduce FBXO32 transcription. Overexpression of LINC00494 elevated NFκB1 expression and enhanced cell migration, invasion and tumorigenesis, but additional overexpression of FBXO32 interfered with the tumorgenicity of ovarian cancer cells and .
Our work demonstrated that LINC00494 promoted ovarian cancer progression by modulating FBXO32 binding with the transcription factor NFκB1. These results provided new insight into the mechanism of ovarian cancer pathogenesis and suggested new therapeutic targets.
卵巢癌是最常见的妇科癌症之一，也是全球女性死亡的重要原因。长链非编码RNA（lncRNAs）被认为是致癌过程中基因表达的关键调控因子，但其对卵巢癌发生发展的影响仍需进一步研究。在本报告中，我们将LINC00494鉴定为卵巢癌中一种新的致癌lncRNA。
生物信息学分析预测了卵巢癌中LINC00494、NFκB1和FBXO32之间的潜在相互作用，通过双荧光素酶报告基因检测、RNA下拉实验、RNA免疫沉淀实验和染色质免疫沉淀实验进行验证。用相关处理过的质粒转染癌细胞，随后进行划痕实验和Transwell实验。将处理后的细胞注射到裸鼠体内建立异种移植模型，以测试LINC00494及其靶基因的作用。
LINC00494和NFκB1在卵巢癌细胞和组织中高表达，而FBXO32低表达。发现LINC00494与NFκB1结合并增加其活性，而NFκB1在FBXO32启动子区域富集，从而降低FBXO32的转录。LINC00494的过表达提高了NFκB1的表达，增强了细胞迁移、侵袭和肿瘤发生能力，但FBXO32的额外过表达则干扰了卵巢癌细胞的致瘤性。
我们的研究表明，LINC00494通过调节FBXO32与转录因子NFκB1的结合促进卵巢癌进展。这些结果为卵巢癌发病机制提供了新的见解，并提出了新的治疗靶点。
