当前位置：
X-MOL 学术
›
Oncogenesis
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1.
Oncogenesis ( IF 5.9 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41389-019-0182-7 Xiaona Zhang 1 , Yanchun Zhou 1 , Shaoying Chen 1 , Wei Li 1 , Weibing Chen 1 , Wei Gu 1, 2
Oncogenesis ( IF 5.9 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41389-019-0182-7 Xiaona Zhang 1 , Yanchun Zhou 1 , Shaoying Chen 1 , Wei Li 1 , Weibing Chen 1 , Wei Gu 1, 2
Affiliation
|
Long noncoding RNA (lncRNA) represents a class of endogenous RNAs that regulate gene expression in eukaryotes. To date, the function and underlying mechanism of the majority of mammalian lncRNAs remain unknown. Here, we report that MACC1-AS1, a cognate antisense lncRNA of the sixth intron of the MACC1 gene, functions as a cell growth modulator and enhances breast tumor progress. RNA pulldown and luciferase assays showed that MACC1-AS1 contained binding sites for multiple miRNAs, including well-known tumor suppressors miR-384 and miR-145-3p that repress the expression of pleiotrophin (PTN) and c-Myc mRNAs. Binding of miR-384 and miR-145-3p miRNAs to MACC1-AS1 alters the cell growth phenotype through increased expression of PTN and c-Myc mRNAs. MACC1-AS1 also competitively interacted with PTBP1, an RNA-binding protein, via a conserved pyrimidine rich motif within this lncRNA. Binding of PTBP1to MACC1-AS1 not only stabilized MACC1-AS1 and enhanced the sponge effect of MACC1-AS1 on miRNAs, but also decreased PTBP1 availability for binding to target mRNAs. Our results define a new dimension into how a lncRNA is able to regulate cell growth by sponging multiple miRNAs and an RNA-binding protein.
中文翻译：
LncRNA MACC1-AS1可以处理多个miRNA和RNA结合蛋白PTBP1。
长非编码RNA（lncRNA）代表了一类内源性RNA，它们调节真核生物中的基因表达。迄今为止，大多数哺乳动物lncRNA的功能和潜在机制仍然未知。在这里，我们报告MACC1-AS1，MACC1基因第六个内含子的同源反义lncRNA，起细胞生长调节剂的作用，并增强了乳腺肿瘤的进展。RNA下拉和荧光素酶分析表明，MACC1-AS1包含多个miRNA的结合位点，包括众所周知的抑癌基因miR-384和miR-145-3p，它们抑制多效性蛋白（PTN）和c-Myc mRNA的表达。miR-384和miR-145-3p miRNA与MACC1-AS1的结合通过增加PTN和c-Myc mRNA的表达来改变细胞生长表型。MACC1-AS1还与RNA结合蛋白PTBP1竞争性相互作用，通过该lncRNA内的保守的富含嘧啶的基序。PTBP1与MACC1-AS1的结合不仅稳定了MACC1-AS1并增强了MACC1-AS1对miRNA的海绵效应，而且还降低了PTBP1与靶mRNA结合的可用性。我们的结果为lncRNA如何通过海绵化多个miRNA和RNA结合蛋白调节细胞生长定义了一个新的维度。
更新日期：2019-12-10
中文翻译：
LncRNA MACC1-AS1可以处理多个miRNA和RNA结合蛋白PTBP1。
长非编码RNA（lncRNA）代表了一类内源性RNA，它们调节真核生物中的基因表达。迄今为止，大多数哺乳动物lncRNA的功能和潜在机制仍然未知。在这里，我们报告MACC1-AS1，MACC1基因第六个内含子的同源反义lncRNA，起细胞生长调节剂的作用，并增强了乳腺肿瘤的进展。RNA下拉和荧光素酶分析表明，MACC1-AS1包含多个miRNA的结合位点，包括众所周知的抑癌基因miR-384和miR-145-3p，它们抑制多效性蛋白（PTN）和c-Myc mRNA的表达。miR-384和miR-145-3p miRNA与MACC1-AS1的结合通过增加PTN和c-Myc mRNA的表达来改变细胞生长表型。MACC1-AS1还与RNA结合蛋白PTBP1竞争性相互作用，通过该lncRNA内的保守的富含嘧啶的基序。PTBP1与MACC1-AS1的结合不仅稳定了MACC1-AS1并增强了MACC1-AS1对miRNA的海绵效应，而且还降低了PTBP1与靶mRNA结合的可用性。我们的结果为lncRNA如何通过海绵化多个miRNA和RNA结合蛋白调节细胞生长定义了一个新的维度。
京公网安备 11010802027423号