ELK1 activated-long noncoding RNA LBX2-AS1 aggravates the progression of ovarian cancer through targeting miR-4784/KDM5C
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ORIGINAL PAPER
ELK1 activated‑long noncoding RNA LBX2‑AS1 aggravates the progression of ovarian cancer through targeting miR‑4784/KDM5C axis Hangzhi Gu1 · Rongrong Lin1 · Feiyun Zheng1 · Qian Zhang1 Received: 16 June 2020 / Accepted: 16 October 2020 © Springer Nature B.V. 2020
Abstract As one of the most common cancers in female, ovarian cancer (OC) has become a serious public burden now. Mounting researches have indicated long noncoding RNAs (lncRNAs) can affect many biological processes including cancer development. LncRNA LBX2-AS1 was identified to be an oncogene in some cancers, but the role of LBX2-AS1 in OC remains to be elucidated. Bioinformatics analysis and experiments including ChIP, RT-qPCR, RIP, luciferase reporter, western blot and CCK-8 were performed to explore the role of LBX2-AS1 in OC. LBX2-AS1 expression was markedly increased in OC tissues and cell lines. Functionally, LBX2-AS1 silencing inhibited cell proliferation, migration and stemness but facilitated cell apoptosis in OC. Moreover, depletion of LBX2-AS1 suppressed tumor growth of OC in vivo. Mechanically, LBX2AS1 was activated by transcriptional factor ELK1. ELK1 enhanced the expression of LBX2-AS1 in OC cells. In addition, miR-4784 was confirmed to be sponged by LBX2-AS1. There was a negative expression correlation between LBX2-AS1 and miR-4784 in OC tissues. Subsequently, KDM5C was identified to be a direct target of miR-4784 in OC cells. KDM5C was negatively regulated by miR-4784 and positively regulated by LBX2-AS1 in terms of expression level. Upregulation of KDM5C reversed the inhibitory effect of LBX2-AS1 depletion on the progression of OC. This study proved that ELK1 activated-LBX2-AS1 aggravated the progression of OC by targeting the miR-4784/KDM5C axis, suggesting that LBX2-AS2 may be a promising diagnostic biomarker of OC. Keywords LBX2-AS1 · ELK1 · miR-4784 · KDM5C · Ovarian cancer
Introduction Ovarian cancer (OC) is the eighth leading cause of cancerrelated death in female worldwide and one of the most frequent types of cancers, which poses a serious threat to public health (Jayson et al. 2014; Siegel et al. 2014). The etiology of OC is involved in genetic and epigenetic factor, but the underlying mechanism remains obscure (Siegel et al. 2014). Up till now, there has been no specific symptoms and effective screening methods for patients with OC, so OC is usually diagnosed in the advanced stages (Mirandola et al. 2011; Zhang et al. 2017a). Although the main treatments for * Qian Zhang [email protected] 1
Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, No. 1 Fuxue Lane, Lucheng District, Wenzhou, Zhejiang, China
OC including surgery, radiotherapy and neoadjuvant chemotherapy are greatly improved, the 5-year survival rate is only 30% (Zhao et al. 2014). Therefore, exploration of novel biomarkers for diagnosis and new therapeutic targets is essential to improve the outcomes in patients with OC. Long noncoding RNAs (lncRNAs) are a category of noncoding RNAs with more than 200 nu
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