hnRNPL-activated circANKRD42 back-splicing and circANKRD42-mediated crosstalk of mechanical stiffness and biochemical signal in lung fibrosis.
hnRNPL-activated circANKRD42 back-splicing and circANKRD42-mediated crosstalk of mechanical stiffness and biochemical signal in lung fibrosis.
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DOI：
10.1016/j.ymthe.2022.01.045
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发表时间：
2022-06-01
影响因子：
12.4
通讯作者：
Song, Xiaodong
中科院分区：
文献类型：
--
作者：
Xu, Pan;Zhang, Jinjin;Wang, Meirong;Liu, Bo;Li, Rongrong;Li, Hongbo;Zhai, Nailiang;Liu, Weili;Lv, Changjun;Song, Xiaodong
增加的环状RNA（circRNA）参与特发性肺纤维化（IPF）的进展。然而，在IPF中，circRNA生物发生和circRNA介导的机械刚度和生化信号之间的串扰仍然不清楚。在这项研究中，从IPF患者的外周血中鉴定了一种新的circRNA-ankyrin repeat domain 42（ANKRD 42），其通过机械刚度和生化信号的密切沟通参与肺纤维化。机制研究表明，异质核核糖核蛋白L（hnRNP L）激活circANKRD 42反向剪接生物合成。生物遗传学circANKRD 42吸收miR-324- 5 p来促进AJUBA表达，从而阻断磷酸化的yes相关蛋白1（YAP 1）与大肿瘤抑制激酶1/2（LATS 1/2）之间的结合，导致进入细胞核的YAP 1增加。circANKRD 42还吸收miR-136- 5 p以促进YAP 1翻译。在细胞核中积累的YAP 1与TEAD结合，从而启动与机械刚度相关的基因的转录。最后，在小鼠中评估circANKRD 42的治疗效果，并在IPF患者中分析circANKRD 42与临床病理特征之间的关联。我们的研究结果支持circANKRD 42是一种有前途的生物标志物，也是IPF治疗中与细胞骨架张力相关的潜在治疗靶点。Song等人报道了肺纤维化相关的circRNA-ANKRD 42，其中反向剪接生物合成被hnRNP L激活。他们还确定了circANKRD 42通过海绵状miR-324- 5 p和miR-136- 5 p介导机械刚度和生化信号的密切沟通，以促进AJUBA和YAP 1。
Increasing circular RNAs (circRNAs) are involved in the progression of idiopathic pulmonary fibrosis (IPF). However, circRNA biogenesis and circRNA-mediated crosstalk between mechanical stiffness and biochemical signals in IPF remain obscure. In this study, a novel circRNA-ankyrin repeat domain 42 (ANKRD42) from peripheral blood of patients with IPF, which participated in pulmonary fibrosis through the close communication of mechanical stiffness and biochemical signals, was identified. Mechanistic studies revealed that the heterogeneous nuclear ribonucleoprotein L (hnRNP L) activated the circANKRD42 reverse splicing biogenesis. The biogenetic circANKRD42 sponged miR-324-5p to promote the AJUBA expression, which blocked the binding between phosphorylated yes-associated protein 1 (YAP1) and large tumor suppressor kinase 1/2 (LATS1/2), leading to increased YAP1 entering the nucleus. circANKRD42 also sponged miR-136-5p to promote the YAP1 translation. Accumulating YAP1 in nucleus bound to TEAD, which initiated the transcription of genes related to mechanical stiffness. Finally, the therapeutic effect of circANKRD42 was evaluated in mice and the association between circANKRD42 and clinicopathological features was analyzed in IPF patients. Our findings supported that circANKRD42 is a promising biomarker and a potential therapeutic target related to cytoskeleton tension for IPF treatment. Song et al. reported a pulmonary-fibrosis-related circRNA-ANKRD42, in which reverse splicing biogenesis was activated by hnRNP L. They also identified circANKRD42 mediated the close communication of mechanical stiffness and biochemical signals through sponging miR-324-5p and miR-136-5p to promote the AJUBA and YAP1.
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影响因子：
64.5
作者：
Kleaveland B;Shi CY;Stefano J;Bartel DP
通讯作者：
Bartel DP
DOI：
10.1016/j.omtn.2021.01.007
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Bu FT;Zhu Y;Chen X;Wang A;Zhang YF;You HM;Yang Y;Yang YR;Huang C;Li J
通讯作者：
Li J
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit
影响因子：
16.8
作者：
Lu, Qing;Li, Jianchao;Zhang, Mingjie
通讯作者：
Zhang, Mingjie
落新妇苷治疗肺纤维化过程中两个 circRNA 和一个 miRNA 及其靶基因的调控网络
影响因子：
5.3
作者：
Lu, Guangping;Zhang, Jinjin;Song, Xiaodong
通讯作者：
Song, Xiaodong