文章：

lncRNA DLX6-AS1上调通过miR-513c/Cul4A/ANXA10轴支持肝细胞癌的进展

Upregulated lncRNA DLX6-AS1 underpins hepatocellular carcinoma progression via the miR-513c/Cul4A/ANXA10 axis 

原文发布日期：2020-12-04 

英文摘要：

Recent studies have illustrated the role of aberrant regulatory interactions in the mediation of malignant phenotypes of cancer cells, which could potentially provide novel therapeutic targets to limit the destructive recurrence and metastasis of hepatocellular carcinoma (HCC). Herein, we clarify the oncogenic role of the long noncoding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) in HCC in vivo and in vitro. To this end, we knocked down lncRNA DLX6-AS1 and manipulated the expression of miR-513c to characterize their effects in HCC cell viability, migration, invasion, and apoptosis. Furthermore, we probed the interactions with miR-513c’s target gene Cullin4A (Cul4A) and the degradation of Annexin A10 (ANXA10) protein. Our data show that lncRNA DLX6-AS1 and Cul4A were highly expressed, while miR-513c and ANXA10 were poorly expressed in HCC tissues and cells. Moreover, the silencing of lncRNA DLX6-AS1 impeded the viability, invasion, and migration of HCC cells, while stimulating cell apoptosis. Further data indicated that lncRNA DLX6-AS1 targeted and repressed miR-513c expression, where the tumor-inhibiting effects of lncRNA DLX6-AS1 silencing was achieved by elevating miR-513c expression. Importantly, the lncRNA DLX6-AS1 upregulated the expression of Cul4A through sponging of miR-513c. The silencing of Cul4A restricted the malignant phenotypes of HCC cells by repressing the ubiquitination-mediated degradation of ANXA10. In vivo experiments verified that lncRNA DLX6-AS1 promoted the progression of HCC through the miR-513c/Cul4A/ANXA10 axis. Thus, the silencing of lncRNA DLX6-AS1 impaired miR-513c-dependent Cul4A inhibition and subsequently elevated ubiquitination-mediated degradation of ANXA10, thereby preventing the occurrence and development of HCC. 

摘要翻译： 

近期研究揭示了异常调控相互作用在介导癌细胞恶性表型中的作用，这为限制肝细胞癌（HCC）破坏性复发和转移提供了潜在治疗靶点。本研究通过体内外实验阐明了长链非编码RNA（lncRNA）DLX6-AS1在HCC中的致癌机制。我们通过敲低lncRNA DLX6-AS1并调控miR-513c表达，系统评估了二者对HCC细胞活力、迁移、侵袭和凋亡的影响，并深入探究了其与miR-513c靶基因Cullin4A（Cul4A）的相互作用及Annexin A10（ANXA10）蛋白降解过程。实验数据显示：在HCC组织和细胞中，lncRNA DLX6-AS1与Cul4A呈高表达，而miR-513c和ANXA10表达显著下调。沉默lncRNA DLX6-AS1可抑制HCC细胞活力、侵袭和迁移能力，同时促进细胞凋亡。机制研究表明，lncRNA DLX6-AS1通过靶向抑制miR-513c表达发挥促癌作用，而其沉默产生的抑瘤效应正是通过上调miR-513c实现。值得注意的是，lncRNA DLX6-AS1通过吸附miR-513c上调Cul4A表达，而沉默Cul4A可通过抑制泛素化介导的ANXA10降解来限制HCC恶性表型。体内实验证实lncRNA DLX6-AS1通过miR-513c/Cul4A/ANXA10轴促进HCC进展。因此，沉默lncRNA DLX6-AS1可通过削弱miR-513c依赖性的Cul4A抑制效应，进而降低泛素化介导的ANXA10降解，最终抑制HCC的发生与发展。

原文链接：

Upregulated lncRNA DLX6-AS1 underpins hepatocellular carcinoma progression via the miR-513c/Cul4A/ANXA10 axis