Liu Weiwei, Cheng Jing
Maternal and Child Health Hospital of Hubei Province, Department of Gynecology, Wuhan, China.
Renmin Hospital of Wuhan University, Department of Obstetrics and Gynecology, Wuhan, China.
Genet Mol Biol. 2022 Jan 31;45(1):e20210224. doi: 10.1590/1678-4685-GMB-2021-0224. eCollection 2022.
The function and mechanism of long intergenic non-protein coding RNA 974 (LINC00974) are rarely reported in ovarian cancer (OC). The study aimed to investigate how LINC00974 affects the progression of OC. The expression levels of LINC00974, microRNA-33a (miR-33a), and high mobility group box 2 (HMGB2) mRNA were detected by qRT-PCR. The LINC00974/miR-33a/HMGB2 axis was confirmed by dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and biotinylated RNA pull-down assays. A series of in vitro experiments were employed to assess the effects of LINC00974/miR-33a/HMGB2 axis on the proliferation, invasion and epithelial mesenchymal transition (EMT) of OC cells. Results showed that LINC00974 and HMGB2 mRNA expression were upregulated in OC cells, while miR-33a expression was downregulated. HMGB2 was a direct target gene of miR-33a. LINC00974 act as a competing endogenous RNA (ceRNA) to directly bind with miR-33a, thereby upregulated HMGB2 expression. Notably, silencing of LINC00974 suppressed cell proliferation, invasion and EMT of OC cells, whereas miR-33a knockdown partially reversed the phenotypes of LINC00974 on OC cells. Overall, our study demonstrated that LINC00974 sponges miR-33a to promote cell proliferation, invasion, and EMT of OC through HMGB2 upregulation. LINC00974/miR-33a/HMGB2 axis may be an important signaling pathway in the progression of OC.
长链基因间非编码RNA 974(LINC00974)在卵巢癌(OC)中的功能和机制鲜有报道。本研究旨在探究LINC00974如何影响OC的进展。通过qRT-PCR检测LINC00974、微小RNA-33a(miR-33a)和高迁移率族蛋白B2(HMGB2)mRNA的表达水平。通过双荧光素酶报告基因、RNA结合蛋白免疫沉淀(RIP)和生物素化RNA下拉实验证实了LINC00974/miR-33a/HMGB2轴。采用一系列体外实验评估LINC00974/miR-33a/HMGB2轴对OC细胞增殖、侵袭和上皮间质转化(EMT)的影响。结果显示,OC细胞中LINC00974和HMGB2 mRNA表达上调,而miR-33a表达下调。HMGB2是miR-33a的直接靶基因。LINC00974作为竞争性内源性RNA(ceRNA)直接与miR-33a结合,从而上调HMGB2表达。值得注意的是,沉默LINC00974可抑制OC细胞的增殖、侵袭和EMT,而敲低miR-33a可部分逆转LINC00974对OC细胞的表型影响。总体而言,我们的研究表明LINC00974通过上调HMGB2促进OC细胞增殖、侵袭和EMT。LINC00974/miR-33a/HMGB2轴可能是OC进展中的重要信号通路。