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

Fan Zhang; Xiu-Xiu Zhang; Jian-Guo Zhang; Kiran Thakur; Jesus Simal-Gandara; Miguel A Prieto; Mohammad Rizwan Khan; Hui Cao; Zhao-Jun Wei

doi:10.1016/j.fct.2023.113900

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

Food Chem Toxicol. 2023 Aug:178:113900. doi: 10.1016/j.fct.2023.113900. Epub 2023 Jun 25.

Authors

Fan Zhang¹, Xiu-Xiu Zhang², Jian-Guo Zhang³, Kiran Thakur⁴, Jesus Simal-Gandara⁵, Miguel A Prieto⁶, Mohammad Rizwan Khan⁷, Hui Cao⁸, Zhao-Jun Wei⁹

Affiliations

¹ School of Life Sciences, Anhui Normal University, Wuhu, 241000, People's Republic of China; School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China; School of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Universidade de Vigo, Ourense, E-32004, Spain. Electronic address: [email protected].
² School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: [email protected].
³ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: [email protected].
⁴ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: [email protected].
⁵ School of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Universidade de Vigo, Ourense, E-32004, Spain. Electronic address: [email protected].
⁶ School of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Universidade de Vigo, Ourense, E-32004, Spain. Electronic address: [email protected].
⁷ Department of Chemistry, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. Electronic address: [email protected].
⁸ School of Analytical Chemistry and Food Science, Nutrition and Bromatology Group, Universidade de Vigo, Ourense, E-32004, Spain. Electronic address: [email protected].
⁹ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: [email protected].

PMID: 37369310
DOI: 10.1016/j.fct.2023.113900

Abstract

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.

Keywords: Asparanin a; Endometrial cancer; High-throughput sequencing; Tumor suppressor; miRNA-6236-p5_4.

MeSH terms

Apoptosis / genetics
Cell Line, Tumor
Cell Proliferation
Endometrial Neoplasms* / drug therapy
Endometrial Neoplasms* / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism

Substances

asparanin A
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
MicroRNAs