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Dysregulated circRNA_100876 suppresses proliferation of osteosarcoma cancer cells by targeting microRNA‐136
Author(s) -
Jin Jian,
Chen Ajuan,
Qiu Weizheng,
Chen Yilin,
Li Qingchu,
Zhou Xinying,
Jin Dadi
Publication year - 2019
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.28837
Subject(s) - cell cycle , cell growth , flow cytometry , cancer research , osteosarcoma , carcinogenesis , gene silencing , microrna , apoptosis , cell , gene knockdown , downregulation and upregulation , chemistry , biology , microbiology and biotechnology , cancer , biochemistry , gene , genetics
The aim of this study was to explore the regulatory mechanism of circRNA_100876/ microRNA‐136 (miR‐136) axis in the development and progression of osteosarcoma cancer. Quantitative real‐time polymerase chain reaction (RT‐qPCR) was used to evaluate the expression levels of circRNA_100876 and miR‐136 in osteosarcoma cancer samples and the adjacent nontumor tissues. Then, cell proliferation, cell cycle, apoptosis, and migration of circRNA_100876‐knocked down cells were analyzed by in vitro and in vivo experiments, using cell counting kit‐8 (CCK‐8), flow cytometry, and transwell and tumorigenesis assays. The expression of circRNA_100876 was found to be significantly upregulated in osteosarcoma, and was closely correlated with the tumor size and tumor differentiation degree. In addition, the knockdown of circRNA_100876 could significantly inhibit the tumor growth, both in vitro and in vivo. Flow cytometry and Western blot analysis results showed that the downregulation of circRNA_100876 inhibited osteosarcoma cells proliferation via promoting apoptosis and arresting more cells in the G2/M stage, as suggested by the expression of apoptosis and cell cycle pathway‐related proteins, which changed consistently. Furthermore, the level of miR‐136 was negatively correlated with the expression of circRNA_100876, and miR‐136 inhibitors were able to reverse the suppression of cell proliferation induced by silencing circRNA_100876. Our study demonstrates that the dysregulation of circRNA_100876 could induce apoptosis and arrest the cell cycle at G2/M stage, followed by suppression of cell proliferation in osteosarcoma, while silencing miR‐136 could restore the cell growth. Therefore, circRNA_100876 might serve as a promising biomarker and treatment target for osteosarcoma.