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Rutin treats myocardial damage caused by pirarubicin via regulating miR‐22‐5p‐regulated RAP1/ERK signaling pathway
Author(s) -
Qin Meng,
Li Qi,
Wang Yadi,
Li Tengteng,
Gu Zehui,
Huang Peng,
Ren Liqun
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22615
Subject(s) - mapk/erk pathway , rap1 , chemistry , signal transduction , apoptosis , microbiology and biotechnology , kinase , in vivo , lyn , protein kinase b , cancer research , pharmacology , proto oncogene tyrosine protein kinase src , biology , biochemistry , genetics
Our experiments have previously demonstrated that rutin (RUT) can improve myocardial damage caused by pirarubicin (THP). However, the underlying molecular mechanisms remain uncertain. In this study, we developed an microRNA (miRNA) chip by replicating the rat model of THP‐induced myocardial injury and identified miR‐22‐5p and the RAP1‐member of RAS oncogene family/extracellular regulated protein kinases (RAP1/ERK) signaling pathway as an object of study. Also, in vivo experiments demonstrated that THP caused abnormal changes in the electrocardiogram, cardiac function, and histomorphology in rats ( P < .01). THP also reduces the expression of miR‐22‐5p ( P < .01) and increases the levels of RAP1/ERK signaling pathway‐related proteins ( P < .01, P < .05). RUT significantly improved THP‐induced myocardial damage ( P < .01), increased the expression of miR‐22‐5p ( P < .01), and decreased the levels of RAP1/ERK signaling pathway‐related proteins ( P < .01, P < .05). In vitro studies confirmed that Rap1a is one of the target genes of miR‐22‐5p. miR‐22‐5p overexpression in cardiomyocytes can affect the RAP1/ERK pathway and reduce reactive oxygen species production and cardiomyocyte apoptosis caused by THP ( P < .01), which is consistent with the effect of RUT. Our results indicate that RUT treats THP‐induced myocardial damage, which may be achieved by upregulating miR‐22‐5p, causing changes in its target gene Rap1a and the RAP1/ERK pathway.