RESUMEN
CONTEXT: Atherosclerosis (AS) is the main cause of cardiovascular and cerebrovascular diseases. Pueraria lobata (Willd.) Ohwi (Fabaceae) has a positive effect on improving these diseases. OBJECTIVE: The P. lobata effect on the proliferation and inflammation of vascular smooth muscle in AS and the potential mechanism were investigated. MATERIALS AND METHODS: By feeding a high-fat diet to 8-week-old apolipoprotein E knockout mice, an atherosclerosis model was created. H&E and IHC staining were used to analyse the histopathology of mice. CCK-8, TUNEL, and scratch tests were used to detect cell proliferation, apoptosis, and migration after 24 h treatment, respectively. ELISA was performed to evaluate the level of IL-6 and IL-8. The target miRNA and its downstream target gene were screened by the bioinformatics method; RT-qPCR has conducted to analyse the expression of these genes. RESULTS: In the aortic tissue and serum of AS mice, puerarin can lower the expression of α-SMA and the inflammatory proteins IL-6 and IL-8. Puerarin (200 M) decreased hVSMC proliferation, migration, and IL-6 and IL-8 secretion by more than half. The inhibitory impact of puerarin on hVSMC was decreased by overexpression of miR-29b-3p. IGF1 was miR-29b-3p's downstream target gene. IGF1 expression increased almost 3-fold in AS mice and hVSMC, but miR-29b-3p mimic inhibited it. The effect of miR-29b-3p on hVSMC was reversed when IGF1 was overexpressed. DISCUSSION AND CONCLUSIONS: Puerarin inhibits the proliferation and inflammation of vascular smooth muscle in AS through the miR-29b-3p/IGF1 pathway. Puerarin may have a beneficial effect in the treatment of atherosclerosis and offer a novel therapy option.
Asunto(s)
Aterosclerosis , MicroARNs , Pueraria , Ratones , Animales , Músculo Liso Vascular/metabolismo , Interleucina-6 , Interleucina-8 , MicroARNs/genética , Proliferación Celular , InflamaciónRESUMEN
Cancer of the colon and rectum are two distinct entities, which require different treatment strategies and separate treatment. MicroRNAs (miRNAs) act as critical regulators of genes involved in several biological processes. Aberrant alterations of miRNAs have been found in several types of cancer, including colon cancer and rectal cancer. Extensive catalogues of downregulated miRNAs have been identified for colon cancer, whereas only limited data are available for rectal cancer. An example of miRNA profiling in a previous study found that miRNA (miR)144 showed aberrant expression and appeared to be rectal cancerspecific, its expression not being reported in colon cancer. In the present study, the role of miR144 in rectal cancer was investigated. SW837 and SW1463 cell lines were selected as rectal cell carcinoma cells. Using reverse transcription-quantitative polymerase chain reaction, western blot, BrdU, cell migration and cell viability assays, it was found that the expression levels of miR144 were significantly reduced in the SW837 and SW1463 cell lines, and the overexpression of miR144 suppressed rectal cancer cell viability, migration and proliferation. In addition, Rhoassociated coiledcoil containing protein kinase 1 (ROCK1) was identified as a target of miR144 in the rectal cancer cells. The supplementation of ROCK1 markedly restored the cell migration and proliferation, which was inhibited by miR144. Together, the data of the present study demonstrated that miR144 acts as a tumor suppressor by targeting ROCK1, and indicates the potential of miR144 as a novel biomarker and target in the treatment of rectal cancer.