RETRACTED: MicroRNA-182 downregulates Wnt/β-catenin signaling, inhibits proliferation, and promotes apoptosis in human osteosarcoma cells by targeting HOXA9 (Retracted Article)

被引:13
作者
Zhang, Zi-Feng [1 ]
Wang, Yong-Jian [1 ]
Fan, Shao-Hua [1 ]
Du, Shi-Xin [2 ]
Li, Xue-Dong [2 ]
Wu, Dong-Mei [1 ]
Lu, Jun [1 ]
Zheng, Yuan-Lin [1 ]
机构
[1] Jiangsu Normal Univ, Sch Life Sci, Key Lab Biotechnol Med Plants Jiangsu Prov, Xuzhou 221116, Peoples R China
[2] Shenzhen Univ, Affiliated Hosp 3, Dept Orthoped, Shenzhen 518002, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA-182; homeobox A9; wingless-type/beta-catenin signaling pathway; osteosarcoma; BETA-CATENIN; LUNG-CANCER; IN-VITRO; EXPRESSION; LEUKEMIA; PATHWAY; ACTIVATION; MIR-182; GENES; BAX;
D O I
10.18632/oncotarget.21167
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We investigated the mechanisms by which microRNA (miR)-182 promotes apoptosis and inhibits proliferation in human osteosarcoma (OS) cells. Levels of miR-182 and Homeobox A9 (HOXA9) expression were compared between human OS and normal cells. Subjects were divided into OS and normal groups. We analyzed the target relationship of miR-182 and Homeobox A9 (HOXA9). Cells were then assigned into blank, negative control, miR-182 mimics, miR-182 inhibitors, siRNA-HOXA9, or and miR-182 inhibitors + siRNA-HOXA9 groups. Cell function was assayed by CCK-8, flow cytometry and wound healing assay. Additionally, we analyzed OS tumor growth in a xenograft mouse model. Dual-luciferase reporter assays indicated miR-182 directly targets HOXA9. Reverse transcription quantitative PCR and western blotting revealed elevated expression of miR-182, WIF-1, BIM, and Bax, and reduced expression of HOXA9, Wnt, beta-catenin, Survivin, Cyclin D1, c-Myc, Mcl-1, Bcl-xL, and Snail in osteosarcoma cells treated with miR-182 mimic or siRNA-HOXA9 as compared to controls. Osteosarcoma cells also exhibited decreased cell proliferation, migration, and tumor growth, and increased apoptosis when treated with miR-182 mimic or siRNA-HOXA9. Correspondingly, in a xenograft mouse model, osteosarcoma tumor volume and growth were increased when cells were treated with miR-182 inhibitor and decreased by miR-182 mimic or siRNA-HOXA9. These results indicate that miR-182 downregulates Wnt/beta-catenin signaling, inhibits cell proliferation, and promotes apoptosis in osteosarcoma cells by suppressing HOXA9 expression.
引用
收藏
页码:101345 / 101361
页数:17
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