Hsa_circ_0002483 inhibited the progression and enhanced the Taxol sensitivity of non-small cell lung cancer by targeting miR-182-5p

被引:100
作者
Li, Xiaoping [1 ]
Yang, Bo [1 ]
Ren, Haixia [2 ]
Xiao, Ting [3 ]
Zhang, Liang [1 ]
Li, Lei [1 ]
Li, Mingjiang [1 ]
Wang, Xuhui [1 ]
Zhou, Honggang [4 ]
Zhang, Weidong [1 ]
机构
[1] Tianjin First Cent Hosp, Dept Thorac Surg, Tianjin 300192, Peoples R China
[2] Tianjin First Cent Hosp, Dept Pharm, Tianjin 300192, Peoples R China
[3] Nankai Univ, State Key Lab Med Chem Biol, Coll Pharm, Tianjin 300350, Peoples R China
[4] Nankai Univ, Tianjin Int Joint Acad Biomed, Coll Pharm, Tianjin Key Lab Mol Drug Res, Tianjin 300350, Peoples R China
关键词
PACLITAXEL; RESISTANCE; EFFICACY;
D O I
10.1038/s41419-019-2180-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In this study, we identified a novel circRNA, circ_0002483, and further investigated its functions in the progression and Taxol resistance of NSCLC. We found that circ_0002483 was expressed at low levels in NSCLC tissues and cell lines. Functional assays indicated that circ_0002483 overexpression significantly inhibited NSCLC cell proliferation and invasion in vitro and in vivo and enhanced the sensitivity of NSCLC cells to Taxol. Mechanistically, circ_0002483 was identified to sponge multiple miRNAs including miR-182-5p (also named miR-182), miR-520q-3p, miR-582-3p, miR-587, and miR-655. In addition, circ_0002483 was also demonstrated to regulate the expression of GRB2, FOXO1, and FOXO3, three target genes of miR-182-5p, by sponging miR-182-5p. Circ_0002483 was demonstrated to inhibit NSCLC progression in vitro and in vivo and enhanced the sensitivity of NSCLC cells to Taxol by sponging miR-182-5p to release the inhibition on GRB2, FOXO1, and FOXO3 mRNAs.
引用
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页数:12
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