Pre-miRNA Hsa-Let-7a-2: a Novel Intracellular Partner of Angiotensin II Type 2 Receptor Negatively Regulating its Signals
International Journal of Biological Sciences
; 18(8):3237-3250, 2022.
Article
in English
| ProQuest Central | ID: covidwho-1842940
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.
Biology--Biotechnology; pre-miRNA; hsa-let-7a-2; AGTR2; Receptors; Toll-like receptors; Arteries; miRNA; Cardiovascular diseases; Vasodilation; MicroRNAs; Peptides; COVID-19; Proteins; Competition; Protein-tyrosine-phosphatase; Inflammation; Plasmids; Tyrosine; Neurodegeneration; RhoA protein; Inflammatory response; Homology; Angiotensin II; Hypertension; Ligands; G protein-coupled receptors; Kinetics; Pathogenesis; Phosphorylation; Coronaviruses; Intracellular; Angiotensin
Search on Google
Collection:
Databases of international organizations
Database:
ProQuest Central
Language:
English
Journal:
International Journal of Biological Sciences
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS