Asparanin A exerts cytotoxicity on human endometrial cancer Ishikawa cells via regulating miR-6236-p5_4 expression

Authors：Zhang, Fan; Zhang, Xiu-Xiu; Zhang, Jian-Guo; Thakur, Kiran; Simal-Gandara, Jesus; Prieto, Miguel A.; Khan, Mohammad Rizwan; Cao, Hui^*; Wei, Zhao-Jun^*

Source：Food and Chemical Toxicology, 2023, 178: 113900.

DOI：10.1016/j.fct.2023.113900

• miRNA-6236-p5_4
• High-throughput sequencing
• Asparanin a
• Endometrial cancer
• Tumor suppressor

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, downregulation 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.