近日,，中國(guó)農(nóng)業(yè)科學(xué)院北京畜牧獸醫(yī)研究所,、華中農(nóng)業(yè)大學(xué)的研究人員發(fā)表了題為“MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene”的文章,，發(fā)現(xiàn)調(diào)控肌細(xì)胞分化的新miRNA分子miRNA-148a，其通過(guò)錨定RhoA/ROCK通路的ROCK1基因調(diào)控肌細(xì)胞分化,，并提出了肌生成中miRNA-148a和ROCK1的網(wǎng)絡(luò)調(diào)控模式,。相關(guān)成果公布在生化領(lǐng)域國(guó)際權(quán)威雜志《生物化學(xué)期刊》（The Journal of Biological Chemistry）上。
細(xì)胞分化是生物個(gè)體和器官發(fā)育的重要生物學(xué)過(guò)程,，骨骼肌是動(dòng)物的主要組織,，其生長(zhǎng)發(fā)育包括肌細(xì)胞的增殖、分化,、融合等多個(gè)生物事件,，揭示其分子調(diào)控機(jī)理是認(rèn)識(shí)骨骼肌發(fā)育、畜禽產(chǎn)肉性狀形成分子機(jī)制的基礎(chǔ),。miRNA是一類(lèi)進(jìn)化上保守的小RNA分子,，研究表明其在肌生成過(guò)程中起重要調(diào)控作用，已發(fā)現(xiàn)的相關(guān)miRNA有miRNA-1,，miRNA-133和miRNA-206等,。本研究新鑒定miRNA-148a為調(diào)控成肌細(xì)胞分化的miRNA分子,，過(guò)表達(dá)或敲低miRNA-148a能顯著促進(jìn)或抑制成肌細(xì)胞C2C12和原代肌細(xì)胞分化，通過(guò)生物信息學(xué)和實(shí)驗(yàn)生物學(xué)相結(jié)合的方法揭示RhoA/ROCK通路的ROCK1基因是miRNA-148a的調(diào)控靶基因,。
文章的通訊作者是中國(guó)農(nóng)業(yè)科學(xué)院北京畜牧獸醫(yī)研究所李奎教授領(lǐng)銜的“中國(guó)農(nóng)業(yè)科學(xué)院優(yōu)秀創(chuàng)新團(tuán)隊(duì)”成員唐中林副研究員,，李奎教授課題組從事動(dòng)物肌肉生長(zhǎng)發(fā)育分子機(jī)制研究近20年，2007年曾在《基因組生物學(xué)》（Genome Biology）雜志發(fā)表中外豬種骨骼肌生長(zhǎng)發(fā)育差異分子機(jī)制解析成果,，本研究是該課題組在動(dòng)物肌肉生長(zhǎng)發(fā)育方面研究的最新成果,。文章的第一作者是來(lái)自華中農(nóng)業(yè)大學(xué)的聯(lián)合培養(yǎng)博士生張晶。
此項(xiàng)研究受?chē)?guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目（NO.30830080）和面上項(xiàng)目（NO.31171192）資助,，全部工作均在課題組內(nèi)完成,。（生物谷Bioon.com）
doi:10.1074/jbc.M111.330381
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MicroRNA-148a promotes myogenic differentiation by targeting the ROCK1 gene
Jing Zhang1, Zheng-zhou Ying2, Zhong-lin Tang2,*, Liang-qi Long1 and Kui Li2
MicroRNAs are evolutionarily conserved small RNAs that post-transcriptionally regulate gene expression and have emerged as critical regulators of skeletal muscle development. Here, we identified miR-148a as a novel myogenic microRNA that mediated myogenic differentiation. The expression levels of miR-148a increased during C2C12 myoblast differentiation. Overexpression of miR-148a significantly promoted myogenic differentiation of both C2C12 myoblast and primary muscle cells. Blocking the function of miR-148a with a 2'-O-methylated antisense oligonucleotide inhibitor repressed C2C12 myoblast differentiation. Using a bioinformatics approach, we identified Rho-associated coiled-coil containing protein kinase 1 (ROCK1), a known inhibitor of myogenesis, as a target of miR-148a. A dual-luciferase reporter assay was used to demonstrate that miR-148a directly targeted the 3'UTR of ROCK1. In addition, the overexpression of miR-148a decreased the protein expression of ROCK1 in C2C12 myoblast and primary muscle cells. Furthermore, ROCK1 inhibition with specific siRNA leaded to accelerated myogenic differentiation progression, underscoring a negative regulatory function of ROCK1 in myogenesis. Therefore, our results revealed a novel mechanism in which miR-148a positively regulates myogenic differentiation via ROCK1 downregulation.
