Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA: Effect of miR-146b-5p and lncRNA-AFAP1-AS1

被引：37

作者：

Zhou, Jingkai ^{[1
]}

Liu, Mei ^{[2
]}

Chen, Yanan ^{[1
]}

Xu, Shansen ^{[1
]}

Guo, Yingjie ^{[3
]}

Zhao, Limei ^{[1
]}

机构：

[1] China Med Univ, Shengjing Hosp, Dept Pharm, Shenyang 110004, Liaoning, Peoples R China

[2] China Med Univ, Sch Pharm, Dept Ion Channel Pharmacol, Shenyang, Liaoning, Peoples R China

[3] Jilin Univ, Natl Engn Lab AIDS Vaccine, Key Lab Mol Enzymol & Engn, Minist Educ,Sch Life Sci, Changchun 130021, Jilin, Peoples R China

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2019年 / 234卷 / 04期

基金：

中国国家自然科学基金;

关键词：

AFAP1-AS1; cucurbitacin B; EGFR; miRNA-146-5p; pancreatic cancer; EPIDERMAL-GROWTH-FACTOR; POOR SURVIVAL; LUNG-CANCER; IN-VITRO; K-RAS; EXPRESSION; MIGRATION; INVASION; INHIBITION; RECEPTOR;

D O I：

10.1002/jcp.27264

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cucurbitacin B (CuB) is a natural tetracyclic triterpene product that displays antitumor activity against a wide variety of cancers. In this study, we explored the antipancreatic cancer activity of CuB via the inhibition of expression of the cancer-related long noncoding RNA, actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1). CuB arrested pancreatic cancer (PC) cells in the G2/M cell cycle phase by suppressingthe expression of AFAP1-AS1. Insights into the mechanisms of competing endogenous RNAs (ceRNAs) gained from bioinformatics analysis and luciferase activity assays showed that the epidermal growth factor receptor (EGFR) and AFAP1-AS1 directly compete for miR-146b-5p binding. CuB-induced high miR-146b-5p expression and inhibited the expression of AFAP1-AS1. In summary, reducing the expression of endogenous AFAP1-AS1 effectively increased the available concentration of miR-146b-5p in PC, whereas miR-146b-5p overexpression prevented the expression of endogenous AFAP1-AS1. In particular, we hypothesized that AFAP1-AS1 might act as a ceRNA, effectively becoming a sponge for miR-146b-5p, thereby activating the expression of the EGFR. Thus, CuB suppresses the proliferation, in vitro and in vivo, ofPC cells through the ceRNA effect of AFAP1-AS1 on miR-146b-5p.

引用

页码：4655 / 4667

页数：13

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