Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway

Fan Zhang; Zhi-Jing Ni; Lei Ye; Yuan-Yuan Zhang; Kiran Thakur; Carlos L Cespedes-Acuña; Jinzhi Han; Jian-Guo Zhang; Zhao-Jun Wei

doi:10.1016/j.fct.2021.112036

Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway

Food Chem Toxicol. 2021 Apr:150:112036. doi: 10.1016/j.fct.2021.112036. Epub 2021 Feb 6.

Authors

Fan Zhang¹, Zhi-Jing Ni², Lei Ye³, Yuan-Yuan Zhang⁴, Kiran Thakur⁵, Carlos L Cespedes-Acuña⁶, Jinzhi Han⁷, Jian-Guo Zhang⁸, Zhao-Jun Wei⁹

Affiliations

¹ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China; School of Environmental Science and Engineering, Anhui Normal University, Wuhu, 241002, People's Republic of China. Electronic address: zffs2012@mail.ahnu.edu.cn.
² Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: lovebear@vip.163.com.
³ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: dqxyyelei@163.com.
⁴ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: 1217461863@qq.com.
⁵ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: kumarikiran@hfut.edu.cn.
⁶ Department of Basic Sciences, University of Bio-Bío, Andrés Bello Avenue, Chillan, Chile. Electronic address: ccespedes@ubiobio.cl.
⁷ College of Biological Science and Technology, Fuzhou University, Fuzhou, 350108, People's Republic of China. Electronic address: hjz419@fzu.edu.cn.
⁸ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: zhangjianguo@hfut.edu.cn.
⁹ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: zjwei@hfut.edu.cn.

PMID: 33561516
DOI: 10.1016/j.fct.2021.112036

Abstract

Asparanin A (AA), a natural compound present in vegetables and medicinal herbs like Asparagus officinalis L., has been investigated extensively for its pharmacological attributes. So far, the effect of AA on endometrial cancer (EC) cell migration and invasion has not been explored. Herein, we elucidated the anti-metastasis mechanism of AA on Ishikawa cells based on miRNA-seq and mRNA-seq integrated analyses. AA treatment led to altered miRNAs expression in Ishikawa cells and inhibited the cell wound healing, cell migration and invasion. Gene Ontology and KEGG enrichment analyses showed that the target genes of different expression miRNAs were significantly enriched in Ras, Rap1 and MAPK signaling pathways. Further verification of these changes via qRT-PCR and Western blot assays in vitro and in vivo demonstrated that AA could suppress human EC cell migration and invasion through Ras/ERK/MAPK pathway. Furthermore, top two miRNAs (miR-6236-p5 and miR-12136_R+8) and top three target genes (KITLG, PDGFD, and NRAS) were identified as functional hub miRNAs and genes through miRNA-target gene network analysis. Our data presented a holistic approach to comprehend the anti-metastatic role of AA in EC after in vitro and in vivo analyses.

Keywords: Asparanin A; Endometrial cancer; Invasion; Migration; mRNA; miRNA.

MeSH terms

Animals
Cell Line, Tumor
Cell Movement / drug effects*
Endometrial Neoplasms / drug therapy*
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism*
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Mice
MicroRNAs
Mitogen-Activated Protein Kinase Kinases / genetics
Mitogen-Activated Protein Kinase Kinases / metabolism
Neoplasm Invasiveness
Neoplasms, Experimental
Saponins / pharmacology*
ras Proteins / genetics
ras Proteins / metabolism*

Substances

MicroRNAs
Saponins
asparanin A
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Kinases
ras Proteins