Liu Leg, Zhang Huan-Huan, Zhang Xian-Ning, Liu Lu-Lu, Chen Ming-Tai
Department of Hematology,The Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
Department of Operating Room,The Affiliated Hospital of Jining Medical University, Jining 272000, Shandong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Apr;32(2):610-616. doi: 10.19746/j.cnki.issn.1009-2137.2024.02.043.
To systematically screen and identify long noncoding RNA (lncRNA) associated with bone marrow adiposity changes in aplastic anemia (AA).
The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened. The expression of candidate lncRNA was verified by qRT-PCR in the adipogenic differentiation model of BM-MSC, BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls.
and were significantly highly expressed in AA BM-MSC, and knock-down of and impaired the adipogenic capacity of AA BM-MSC. PPARγ and C/EBPα cotranscriptionally activate promoter activity in binding sites dependant manner. The was also aberrantly highly expressed in AA BM-MSC compared with controls.
and are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC, and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating expression.
系统筛选并鉴定与再生障碍性贫血(AA)骨髓脂肪化改变相关的长链非编码RNA(lncRNA)。
通过生物信息学分析ChIPBase中的PPARγ和C/EBPα ChIP-Seq数据,筛选受PPARγ和C/EBPα共转录调控的潜在lncRNA。通过qRT-PCR在BM-MSC成脂分化模型、感染慢病毒-shPPARγ和慢病毒-shC/EBPα的BM-MSC以及来自AA和对照的临床BM-MSC样本中验证候选lncRNA的表达。
[具体lncRNA名称1]和[具体lncRNA名称2]在AA BM-MSC中显著高表达,敲低[具体lncRNA名称1]和[具体lncRNA名称2]会损害AA BM-MSC的成脂能力。PPARγ和C/EBPα以结合位点依赖的方式共转录激活[具体lncRNA名称3]启动子活性。与对照相比,[具体lncRNA名称3]在AA BM-MSC中也异常高表达。
[具体lncRNA名称1]和[具体lncRNA名称2]在AA BM-MSC中异常表达,可能促进AA BM-MSC的成脂分化,并在一定程度上通过转录激活[具体lncRNA名称3]表达介导骨髓脂肪化改变。