circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.

circFLT1 and lncCCPG1 Sponges miR-93 to Regulate the Proliferation and Differentiation of Adipocytes by Promoting lncSLC30A9 Expression.
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circFLT1和lncCCPG1海绵miR-93通过促进lncSLC30A9表达来调节脂肪细胞的增殖和分化

DOI:
10.1016/j.omtn.2020.09.011
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发表时间:
2020-12-04
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Lan X
Lan X
中科院分区:
其他
文献类型:
--
作者:
Kang Z;Zhang S;Jiang E;Wang X;Wang Z;Chen H;Lan X

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尽管在脂肪细胞中发现了许多环状RNA(CircRNAs)和长非编码RNA(LncRNAs),但它们的确切功能和分子机制仍然知之甚少。基于已有的牛脂肪细胞CircRNA和LncRNA测序数据,我们筛选了CircFlt1和lncCCPG1在前脂肪细胞和脂肪细胞中的差异表达,并进一步分析了它们在脂肪形成过程中的功能和调控。CircFlt1和lncCCPG1的过表达共同促进了脂肪细胞的分化,抑制了其增殖。计算表明,CircFlT1和lncCCPG1与miR-93有多个潜在的结合位点。此外,荧光素酶报告实验证实,CircFlt1和lncCCPG1可能与miR-93相互作用。我们还证明了过表达的miR-93有效地抑制了lncSLC30A9的表达。信号通路分析、荧光素酶活性分析和表达分析表明,lncSLC30A9通过抑制AKT蛋白的表达抑制细胞增殖,通过将FOS蛋白募集到PPARG启动子促进细胞分化。综上所述,我们的结果阐明了cicFlt1和lncCCPG1作为miR-93海绵在牛脂肪细胞中的调节机制。脂肪生成是一个复杂而精细的程序化调控过程,涉及一系列非编码RNA。在这项研究中,作者阐明了CircFlt1和lncCCPG1作为miR-93海绵在牛脂肪细胞中的调节机制。
Although many circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been discovered in adipocytes, their precise functions and molecular mechanisms remain poorly understood. Based on existing circRNA and lncRNA sequencing data of bovine adipocytes, we screened for the differential expression of circFLT1 and lncCCPG1 in preadipocytes and adipocytes and further analyzed their function and regulation during adipogenesis. The overexpression of circFLT1 and lncCCPG1 together facilitated adipocyte differentiation and suppressed proliferation. Computationally, the RNA hybrid showed that circFLT1 and lncCCPG1 had multiple potential binding sites with miR-93. Additionally, luciferase reporting experiments verified that circFLT1 and lncCCPG1 may interact with miR-93. We also demonstrated that overexpressed miR-93 effectively suppresses the expression of lncSLC30A9. Signaling pathway enrichment analysis, luciferase activity assay, and expression analysis revealed that lncSLC30A9 inhibits proliferation by inhibiting the expression of AKT protein and promotes differentiation by recruiting the FOS protein to the promoter of peroxisome proliferator-activated receptor gamma (PPARG). In sum, our results elucidate the regulatory mechanisms of circFLT1 and lncCCPG1 as miR-93 sponges in bovine adipocytes. Adipogenesis is a complex and delicate programmed regulatory process involving a series of non-coding RNAs. In this study, the authors elucidate the regulatory mechanisms of circFLT1 and lncCCPG1 as miR-93 sponges in bovine adipocytes.
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