小鼠正常黑素细胞和小鼠B16黑素瘤细胞的环状RNAs表达谱  

Circular RNA Profiling of Murine Normal Melanocytes and Murine B16 Melanoma Cells

作　　者：魏希扬 汪郑州 姬凯元 WEI Xi-Yang;WANG Zheng-Zhou;JI Kai-Yuan(Anhui Key Laboratory of Genetic Resources Protection and Biological Breeding for Livestock and Poultry,Anhui Agricultural University,Hefei 230036,China)

机构地区：[1]安徽农业大学安徽省畜禽遗传资源保护与生物育种重点实验室,合肥230036

出　　处：《中国生物化学与分子生物学报》2022年第12期1714-1725,共12页Chinese Journal of Biochemistry and Molecular Biology

基　　金：安徽省高校自然科学研究项目(No.KJ2019A0165);安徽省自然科学基金(No.2008085QC158)资助。

摘　　要：黑素瘤是一种多发于皮肤的恶性肿瘤,因其侵袭性强,预后差等特点一直是科研人员关注的热点。环状RNAs(circRNAs)是一种新型内源性非编码RNA,广泛参与动物生长发育、细胞分化和信号转导等生理过程,但circRNAs在黑素瘤细胞内的分子机制尚未被充分解析。本研究以小鼠(C57BL/6J)正常黑素细胞及B16黑素瘤细胞为研究对象,采用二代测序技术分析两种细胞间circRNAs表达特性。测序结果显示,小鼠正常黑素细胞和黑素瘤细胞中共有851个circRNAs,其中195个差异表达circRNAs(DECs)。GO及KEGG数据库注释发现,DECs的来源基因主要参与细胞周期(cell cycle)、紧密结合(tight junction)、Rap1信号通路(Rap1 signaling pathway)、TGF-beta信号通路(TGF-beta signaling pathway)等与细胞增殖、迁移相关的信号通路;探究发现,黑素瘤细胞中显著性高表达的circE2F5(circ-3:14578602|14606309)通过上调E2F5的表达促进黑素瘤细胞增殖。circRNA靶基因预测发现,73个DECs存在miRNA的结合位点,多个潜在靶向miRNAs参与黑素细胞增殖和迁移等过程。本研究通过对DECs来源基因功能注释、DECs靶向miRNAs预测,获得多个与黑素瘤细胞增殖和迁移相关的DECs,期望为黑素瘤研究提供新的见解。Melanoma is a malignant tumor that occurs frequently in the skin. Due to its strong invasiveness and poor prognosis, it has always been the researchers’ focus. Circular RNAs(circRNAs) are novel endogenous non-coding RNAs, which are widely involved in animal growth and development, cell differentiation, signal transduction and other physiological processes. However, the molecular mechanism of circRNAs in melanoma cells has not been fully analyzed. In this study, mice(C57 BL/6 J) normal melanocytes and B16 melanoma cells were used as research objects, and the expression characteristics of circRNAs between the two kinds of cells were analyzed by second-generation sequencing technology. Sequencing results showed that there were 851 circRNAs and 195 differentially expressed circRNAs(DECs) in mouse normal and melanoma cells. GO and KEGG database annotation found that the source genes of DECs were mainly involved in the cell cycle, the tight junction, the Rap1 signaling pathway, the TGF-beta signaling pathway and other signaling pathways related to cell proliferation and migration. CircE2 F5(circ-3:14578602|14606309) was significantly overexpressed in melanoma cells compared with normal melanocyte, which could increase E2 F5 expression, promote the melanoma cell proliferation. TargetScan 7.0 and RegRNA 2.0 predicted that there were 73 DECs in mouse normal melanocytes and melanoma cells that had miRNA binding sites, and multiple potentially targeted miRNAs were involved in the proliferation and migration of melanocytes. In sum, multiple DECs related to melanoma cell proliferation and migration were obtained by functional annotation of DEC source genes and potential targeted miRNAs of DECs, and we expected it to provide new insights for melanoma research.

关 键 词：环状RNA 黑素瘤细胞 细胞增殖 细胞迁移 

分 类 号：S852[农业科学—基础兽医学]