miRNA 表达的全球变化表明通过抑制成纤维细胞中的 miR-222-3p 可提高诱导的乳腺上皮细胞的重编程效率。
Global changes of miRNA expression indicates an increased reprogramming efficiency of induced mammary epithelial cells by repression of miR-222-3p in fibroblasts.
机构信息
Guangxi Key Laboratory of Eye Health, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Guangxi University, School of Animal Science and Technology, Nanning, Guangxi, China.
出版信息
PeerJ. 2024 Jul 12;12:e17657. doi: 10.7717/peerj.17657. eCollection 2024.
BACKGROUND
Our previous studies have successfully reported the reprogramming of fibroblasts into induced mammary epithelial cells (iMECs). However, the regulatory relationships and functional roles of MicroRNAs (miRNAs) in the progression of fibroblasts achieving the cell fate of iMECs are insufficiently understood.
METHODS
First, we performed pre-and post-induction miRNAs sequencing analysis by using high-throughput sequencing. Following that, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were used to determine the primary roles of the significantly distinct miRNAs and targeted genes. Finally, the effect of miR-222-3p on iMECs fate reprogramming by transfecting.
RESULTS
As a result goat ear fibroblasts (GEFs) reprogramming into iMECs activates a regulatory program, involving 79 differentially expressed miRNAs. Besides, the programming process involved changes in multiple signaling pathways such as adherens junction, TGF-β signaling pathway, GnRH secretion and the prolactin signaling pathway, . Furthermore, it was discovered that the expression of miR-222-3p downregulation by miR-222-3p inhibitor significantly increase the reprogramming efficiency and promoted lipid accumulation of iMECs.
背景
我们之前的研究成功地将成纤维细胞重编程为诱导型乳腺上皮细胞（iMECs）。然而，miRNAs（miRNAs）在成纤维细胞获得 iMECs 细胞命运的过程中的调控关系和功能作用还不够清楚。
方法
首先，我们通过高通量测序进行了诱导前后 miRNAs 测序分析。之后，通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集研究，确定了显著差异 miRNAs 和靶向基因的主要作用。最后，通过转染 miR-222-3p 来研究 miR-222-3p 对 iMECs 命运重编程的影响。
结果
结果表明，山羊耳成纤维细胞（GEFs）重编程为 iMECs 会激活一个调控程序，涉及 79 个差异表达的 miRNAs。此外，该编程过程涉及多个信号通路的变化，如黏着连接、TGF-β信号通路、GnRH 分泌和催乳素信号通路。此外，研究发现，miR-222-3p 抑制剂下调 miR-222-3p 的表达，显著提高了 iMECs 的重编程效率，并促进了 iMECs 的脂质积累。
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