miRNA repertoires of ex-vivo bronchial, nasal, and polyps cells cultured from healthy and CF donors. miRNA repertoires of ex-vivo bronchial, nasal, and polyps cells cultured from healthy and CF donors

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic lung disease. Small non-coding RNAs are key regulators of gene expression and participate in various processes, which are dysregulated in CF; however, they remain poorly studied. Here, we determined the complete microRNAs (miRNAs) expression pattern in three CF ex-vivo models. The miRNA profiles of air-liquid interface cultures of airway epithelia (bronchi, nasal cells, and nasal polyps) samples from patients with CF and non-CF controls were obtained by deep sequencing. Compared with non-CF controls, several miRNAs were deregulated in CF samples, for instance miR-181a-5p and the miR-449 family were upregulated. Moreover, mature miRNAs often showed variations (i.e., isomiRs) relative to their reference sequence, such as miR-101, suggesting that miRNAs consist of heterogeneous repertoires of multiple isoforms with different effects on gene expression. Analysis of miR-181a-5p and miR-101-3p roles indicated that they regulate the expression of WISP1, a key component of cell proliferation/migration programs. We showed that miR-101 and miR-181a-5p participated in aberrant recapitulation of wound healing programs by controlling WISP1 mRNA and protein level. Our miRNA expression data bring new insights into CF physiopathology and define new potential therapeutic targets in CF Overall design: miRNA expression profile of NCF and CF cells from Nasal, Polyps and Bronchial cells

囊性纤维化（Cystic fibrosis, CF）是一种遗传性疾病，以慢性肺部病变为典型特征。小型非编码RNA（small non-coding RNAs）是基因表达的关键调控因子，参与多种生理过程，且在CF中存在表达失调，但目前对其研究仍较为匮乏。本研究明确了三种CF离体模型中微小RNA（microRNAs, miRNAs）的完整表达谱。研究通过深度测序获取了CF患者与非CF对照者的气道上皮气液界面培养样本（包含支气管细胞、鼻腔细胞及鼻息肉样本）的miRNA表达谱。与非CF对照相比，CF样本中有多种miRNA出现表达失调，例如miR-181a-5p与miR-449家族均呈现上调表达。此外，成熟miRNA通常会相对于参考序列产生序列变异（即miRNA异构体，isomiRs），以miR-101为例，这表明miRNA由多种具有不同基因表达调控功能的异构体组成异质性库。对miR-181a-5p与miR-101-3p的功能分析显示，二者可调控WISP1的表达，而WISP1是细胞增殖/迁移程序的关键组分。本研究证实，miR-101与miR-181a-5p可通过调控WISP1的mRNA及蛋白水平，参与异常重演的伤口愈合程序。本研究的miRNA表达数据为CF的病理生理学研究提供了新见解，并确立了CF潜在的新型治疗靶点。整体实验设计：取自鼻腔、鼻息肉及支气管组织的非CF（NCF）细胞与CF细胞的miRNA表达谱。