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长链非编码RNA通过调控基于RNA的网络在葡萄膜黑色素瘤中发挥癌基因作用。

LncRNA Acts as an Oncogene in Uveal Melanoma by Regulating an RNA-Based Network.

作者信息

Barbagallo Cristina, Caltabiano Rosario, Broggi Giuseppe, Russo Andrea, Puzzo Lidia, Avitabile Teresio, Longo Antonio, Reibaldi Michele, Barbagallo Davide, Di Pietro Cinzia, Purrello Michele, Ragusa Marco

机构信息

Department of Biomedical and Biotechnological Sciences-Section of Biology and Genetics, University of Catania, 95123 Catania, Italy.

Department of Medical, Surgical Sciences and Advanced Technologies G.F, Ingrassia-Section of Anatomic Pathology, University of Catania, 95123 Catania, Italy.

出版信息

Cancers (Basel). 2020 Dec 21;12(12):3867. doi: 10.3390/cancers12123867.

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults; little is known about the contribution of non-coding RNAs (ncRNAs) to UM pathogenesis. Competitive endogenous RNA (ceRNA) networks based on RNA-RNA interactions regulate physiological and pathological processes. Through a combined approach of in silico and experimental biology, we investigated the expression of a set of long non-coding RNAs (lncRNAs) in patient biopsies, identifying as a potential oncogene in UM. The detection of dysregulation associated with several in vitro functional assays allowed us to investigate its ceRNA regulatory network and shed light on its potential involvement in cancer-related processes, such as epithelial to mesenchymal transition (EMT) and CoCl-induced hypoxia-like response. In vitro transient silencing of impaired cell proliferation and migration, and affected mRNA expression of , , , , and . A "miRNA sponge" and "miRNA protector" model have been hypothesized for -induced regulation of mRNAs. In vitro inhibition of suggested its role as a potential activator of expression. Comprehensively, may be considered a new oncogene in UM and a potential target for RNA-based therapeutic approaches.

摘要

葡萄膜黑色素瘤(UM)是成人中最常见的原发性眼内恶性肿瘤;关于非编码RNA(ncRNAs)在UM发病机制中的作用知之甚少。基于RNA-RNA相互作用的竞争性内源RNA(ceRNA)网络调节生理和病理过程。通过计算机模拟和实验生物学相结合的方法,我们研究了一组长链非编码RNA(lncRNAs)在患者活检组织中的表达,确定 为UM中的一种潜在癌基因。检测到 失调与几种体外功能测定相关,这使我们能够研究其ceRNA调控网络,并揭示其在癌症相关过程中的潜在作用,如上皮-间质转化(EMT)和CoCl诱导的缺氧样反应。体外瞬时沉默 会损害细胞增殖和迁移,并影响 、 、 、 和 的mRNA表达。已经假设了一种“miRNA海绵”和“miRNA保护剂”模型用于 诱导的mRNA调控。体外抑制 表明其作为 表达潜在激活剂的作用。综合来看, 可能被认为是UM中的一种新癌基因和基于RNA的治疗方法的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/154c/7767460/cc514850d7c1/cancers-12-03867-g001.jpg

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