LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis

LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis
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DOI:
10.18632/aging.102325
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发表时间:
2019-10-15
期刊:
影响因子:
5.2
通讯作者:
Zhu, Xiaodong
Zhu, Xiaodong
中科院分区:
医学2区
文献类型:
--
作者:
Fu, Dong;Lu, Chunwen;Zhu, Xiaodong

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目的:目的探讨长链非编码RNA(lncRNA)TTN-AS 1通过microRNA miR-134- 5 p/malignant brain tumor domain containing 1(MBTD 1)轴调控骨肉瘤细胞凋亡和耐药的机制。lncRNA TTN-AS 1促进细胞活力并抑制凋亡。miR-134- 5 p靶向MBTD 1,其受lncRNA TTN-AS 1调节。MBTD 1在骨肉瘤中高表达,与预后不良有关。MBTD 1促进细胞活力并抑制细胞凋亡,MBTD 1的敲低逆转了lncRNA TTN-AS 1的促癌作用。结论:在骨肉瘤中,lncRNA TTN-AS 1通过靶向miR-134- 5 p促进MBTD 1的表达,调节细胞生长、凋亡和耐药。应用质粒转染技术沉默或过表达lncRNA TTN-AS 1、miR-134- 5 p和MBTD 1。Western blotting和定量聚合酶链反应(qPCR)分别检测蛋白质和RNA。采用CCK-8细胞计数试剂盒和流式细胞仪检测细胞活力和凋亡。采用肿瘤负荷试验研究了lncRNA TTN-AS 1和MBTD 1对骨肉瘤的体内作用。
Aim: To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 (MBTD1) axis.Results: The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.Conclusion: In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.Methods: The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.