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miR‐449c‐5p availability is antagonized by circ‐NOTCH1 for MYC‐induced NOTCH1 upregulation as well as tumor metastasis and stemness in gastric cancer
Author(s) -
Zhao Xiaoyong,
Zhong Qinggui,
Cheng Xueyan,
Wang Shang,
Wu Ruiqing,
Leng Xinling,
Shao Lei
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29575
Subject(s) - downregulation and upregulation , cancer research , gene knockdown , metastasis , cancer , malignancy , microrna , cancer stem cell , biology , medicine , chemistry , gene , genetics
Gastric cancer (GC), identified as the most common gastrointestinal malignancy, is one of the primary causes of cancer‐related mortality in the world. Although surgery and chemotherapy for GC treatment have been improved, the 5‐year overall survival rate is still unsatisfactory. Circ‐NOTCH1 is a novel circular RNA derived from its host gene NOTCH1, and has not been studied in any cancers. Here we explored the potential role and mediatory mechanism of circ‐NOTCH1 in GC. In this study, circ‐NOTCH1 exhibited increased expression in GC tissues and cells. Suppression of circ‐NOTCH1 inhibited cell migration, invasion, tumor spheroids number, and side population ratio. Circ‐NOTCH1 also promoted GC growth and metastasis in vivo. Additionally, it was found that circ‐NOTCH1 could bind to miR‐449c‐5p. Circ‐NOTCH1 promoted metastasis and stemness in GC through sponging miR‐449c‐5p. Subsequently, MYC was identified as a downstream gene of miR‐449c‐5p. MYC could bind to the promoter of NOTCH1 to regulate GC progression. Furthermore, rescue assays demonstrated that NOTCH1 knockdown reversed the effects of overexpression of MYC in metastasis and stemness in AGS cells/sh‐circNOTCH1. Above findings explained that circ‐NOTCH1 promoted metastasis and stemness in GC by targeting miR‐449c‐5p/MYC/NOTCH1 axis, suggesting the possibility of circ‐NOTCH1 as a therapeutic marker for GC.