Asparanin A exerts cytotoxicity on human endometrial cancer Ishikawa cells via regulating miR-6236-p5_4 expression.
Fan ZhangXiu-Xiu ZhangJian-Guo ZhangKiran ThakurJesus Simal-GandaraMiguel A PrietoMohammad Rizwan KhanHui CaoZhao-Jun WeiPublished in: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2023)
miRNAs are emerging as a novel proto-oncogene or tumor suppressor in the initiation and progression of cancer. Several plants naturally contain asparanin A (AA), which has potent anticancer properties. Previously, we discovered that AA exposure increased the expression of miR-6236-p5_4 and caused cytotoxicity in endometrial carcinoma (EC) Ishikawa cells. Herein, the regulation mechanism of miR-6236-p5_4 in the anticancer activity of AA in EC was investigated. Our results showed that the overexpressed miR-6236-p5_4 contributed to modulating cell viability and cell cycle arrest, triggering cell apoptosis, and suppressing migration. Conversely, down-regulation of miR-6236-p5_4 attenuated the anti-cancer effect of AA. Additionally, the PI3K-Akt, p53, Ras, and Rap1 signaling pathways were demonstrated to be the key pathways, whereas CDK6, PIK3CB, and KRAS were found to be directly functional target genes. Our findings imply that miRNA-6236-p5_4 can act as both a molecular diagnostic for the clinical identification and prognosis of EC and a tumor suppressor in AA against EC.
Keyphrases
- cell cycle arrest
- pi k akt
- endometrial cancer
- signaling pathway
- cell death
- induced apoptosis
- poor prognosis
- cell proliferation
- endothelial cells
- binding protein
- cell cycle
- oxidative stress
- papillary thyroid
- mass spectrometry
- genome wide
- epithelial mesenchymal transition
- bioinformatics analysis
- high resolution
- dna methylation
- atomic force microscopy
- high speed