Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression

Zhiyong Lai; Yang Yang; Chaobing Wang; Wenhui Yang; Yichao Yan; Zhu Wang; Jun Xu; Kewei Jiang

doi:10.1080/15384101.2019.1618122

Circular RNA 0047905 acts as a sponge for microRNA4516 and microRNA1227-5p, initiating gastric cancer progression

Cell Cycle. 2019 Jul;18(14):1560-1572. doi: 10.1080/15384101.2019.1618122. Epub 2019 Jun 4.

Authors

Zhiyong Lai¹, Yang Yang², Chaobing Wang², Wenhui Yang³, Yichao Yan⁴, Zhu Wang⁵, Jun Xu¹, Kewei Jiang⁵

Affiliations

¹ a Department of General Surgery , Shanxi Dayi Hospital, Shanxi Academy of Medical Sciences , Taiyuan , Shanxi , People's Republic of China.
² b Department of Breast Center , Peking University People's Hospital , Beijing , People's Republic of China.
³ c Department of Biochemistry and Molecular Biology , Shanxi Medical University , Taiyuan , People's Republic of China.
⁴ d Department of Gastroenterological Surgery , Peking University International Hospital , Beijing , People's Republic of China.
⁵ e Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research , Peking University People's Hospital , Beijing , People's Republic of China.

Abstract

Several lines of evidence suggest that circular RNAs (circRNAs) play important roles in oncogenesis and tumor progression. However, our knowledge of the role of circRNAs in gastric cancer (GC) remains limited. We investigated the possibility that circular RNA 0047905 (circRNA0047905) might act as a tumor promoter in the pathogenesis of gastric cancer by profiling miRNA expression in GC tissues and paired noncancerous mucosa tissues using miRNA microarrays. Next, a ceRNA network was constructed according to common miRNAs binding circRNAs and mRNAs. Mechanistically, we demonstrated that circRNA0047905 directly binds miR4516 and miR1227-5p, relieving suppression for targets SERPINB5 and MMP11. We observed that down-regulated circRNA0047905 expression in gastric cancer cells inhibited Akt/CREB signaling pathway activation. RNA scope in situ hybridization revealed expression of circRNA0047905 in GC. Our data suggest that circRNA0047905 is a promising target for GC diagnosis and therapy.

Keywords: circRNA0047905; competing endogenous RNA; gastric cancer; oncogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis / genetics
Carcinogenesis / metabolism*
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / metabolism
Down-Regulation
Gene Expression Regulation, Neoplastic / genetics
Humans
Matrix Metalloproteinase 11 / genetics
Matrix Metalloproteinase 11 / metabolism
MicroRNAs / genetics
MicroRNAs / metabolism*
Microarray Analysis
Prognosis
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
RNA, Circular / genetics
RNA, Circular / metabolism*
Serpins / genetics
Serpins / metabolism
Signal Transduction / genetics
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism*
Stomach Neoplasms / pathology

Substances

CREB1 protein, human
Cyclic AMP Response Element-Binding Protein
MicroRNAs
RNA, Circular
SERPIN-B5
Serpins
Proto-Oncogene Proteins c-akt
MMP11 protein, human
Matrix Metalloproteinase 11

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China [81702336], the National High-tech R&D Program (863 Program) [2015AA020110] and the Leading Clinical Department Sponsored By '136' Healthcare Improvement Project of Shanxi Province.