Int J Biol Sci 2022; 18(8):3237-3250. doi:10.7150/ijbs.70455 This issue

Research Paper

Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals

Xiaoyan Liu1*, Zhenzhen Chen2*, Shuangyue Li2*, Ling Jin3, Xiao Cui2, Changting Cui2, Yue Deng2, Qiannan Gao2, Luyun Fan2, Yaping Niu2, Wenjie Wang2, Chunmei Cui3, Jiuchang Zhong1, Qinghua Cui3✉, Bin Geng2✉, Jun Cai2✉

1. Department of Cardiology, Heart Center, Beijing Key Laboratory of Hypertension Research, Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
2. Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing 100037, China.
3. Department of Biomedical Informatics, School of Basic Medical Sciences, Center for Non-Coding RNA Medicine, Third Hospital, Peking University, Beijing 100191, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Liu X, Chen Z, Li S, Jin L, Cui X, Cui C, Deng Y, Gao Q, Fan L, Niu Y, Wang W, Cui C, Zhong J, Cui Q, Geng B, Cai J. Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals. Int J Biol Sci 2022; 18(8):3237-3250. doi:10.7150/ijbs.70455. Available from

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Graphic abstract

G protein-coupled receptors (GPCRs) are the largest family of druggable targets, and their biological functions depend on different ligands and intracellular interactomes. Some microRNAs (miRNAs) bind as ligands to RNA-sensitive toll-like receptor 7 to regulate the inflammatory response, thereby contributing to the pathogenesis of cancer or neurodegeneration. It is unknown whether miRNAs bind to angiotensin II (Ang II) type 2 receptor (AGTR2), a critical protective GPCR in cardiovascular diseases, as ligands or intracellular interactomes. Here, screening for miRNAs that bind to AGTR2, we identified and confirmed that the pre-miRNA hsa-let-7a-2 non-competitively binds to the intracellular third loop of AGTR2. Functionally, intracellular hsa-let-7a-2 overexpression suppressed the Ang II-induced AGTR2 effects such as cAMP lowering, RhoA inhibition, and activation of Src homology 2 domain-containing protein-tyrosine phosphatase 1, whereas hsa-let-7a-2 knockdown enhanced these effects. Consistently, overexpressed hsa-let-7a-2 restrained the AGTR2-induced antiproliferation, antimigration, and proapoptosis of cells, and vasodilation of mesenteric arteries. Our findings demonstrated that hsa-let-7a-2 is a novel intracellular partner of AGTR2 that negatively regulates AGTR2-activated signals.

Keywords: pre-miRNA, hsa-let-7a-2, AGTR2