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通过下调靶向微小RNA-143的长链非编码RNA结肠癌相关转录本2抑制骨肉瘤细胞的增殖和转移。

Inhibiting proliferation and metastasis of osteosarcoma cells by downregulation of long non-coding RNA colon cancer-associated transcript 2 targeting microRNA-143.

作者信息

Bi Fengjiang, Chen Can, Fu Jing, Yu Lei, Geng Jia

机构信息

Department of Orthopedics, The First Hospital of Qiqihaer, Qiqihaer, Heilongjiang 161005, P.R. China.

出版信息

Oncol Lett. 2021 Apr;21(4):265. doi: 10.3892/ol.2021.12526. Epub 2021 Feb 8.

Abstract

Osteosarcoma is a malignant bone tumor, which has a high incidence in children and adolescents. However, the pathogenesis of osteosarcoma remains unclear. Long noncoding RNA (lncRNA) is a new potential therapeutic target and diagnostic biomarker for osteosarcoma. Hence, the present study aimed to explore the effect of lncRNA colon cancer-associated transcript (CCAT2) on osteosarcoma and its potential underlying mechanisms. For this purpose, the proliferation of osteosarcoma cells was measured using the CCK-8 assay. The scratch-wound and cell invasion assays were used to determine the migration and invasion of osteosarcoma cells, respectively. LncRNA CCAT2 and microRNA (miR)-143 binding sites were identified by the dual-luciferase reporter assay. RNA and protein expression levels were detected by reverse-transcription quantitative PCR and western blotting, respectively. Downregulation of lncRNA CCAT2 inhibited the proliferation, migration, and invasion of osteosarcoma cells. The findings also revealed that miR-143 bound directly to lncRNA CCAT2. The expression of miR-143 was upregulated by the knockdown of lncRNA CCAT2. Downregulation of the FOS-like antigen 2 was also observed after knockdown of lncRNA CCAT2. The function of lncRNA CCAT2 in osteosarcoma cells was attenuated by co-transfection with anti-miR-143 oligodeoxyribonucleotide. In conclusion, downregulation of lncRNA CCAT2 inhibited the proliferation and metastasis of osteosarcoma cells by targeting miR-143. lncRNA CCAT2 was identified as a potential target for osteosarcoma treatment.

摘要

骨肉瘤是一种恶性骨肿瘤,在儿童和青少年中发病率较高。然而,骨肉瘤的发病机制仍不清楚。长链非编码RNA(lncRNA)是骨肉瘤新的潜在治疗靶点和诊断生物标志物。因此,本研究旨在探讨长链非编码RNA结肠癌相关转录本(CCAT2)对骨肉瘤的影响及其潜在机制。为此,采用CCK-8法检测骨肉瘤细胞的增殖情况。划痕伤口实验和细胞侵袭实验分别用于测定骨肉瘤细胞的迁移和侵袭能力。通过双荧光素酶报告基因实验鉴定lncRNA CCAT2与微小RNA(miR)-143的结合位点。分别通过逆转录定量PCR和蛋白质印迹法检测RNA和蛋白质表达水平。lncRNA CCAT2的下调抑制了骨肉瘤细胞的增殖、迁移和侵袭。研究结果还显示,miR-143直接与lncRNA CCAT2结合。lncRNA CCAT2的敲低上调了miR-143的表达。lncRNA CCAT2敲低后还观察到FOS样抗原2的表达下调。与抗miR-143寡脱氧核苷酸共转染可减弱lncRNA CCAT2在骨肉瘤细胞中的功能。总之,lncRNA CCAT2的下调通过靶向miR-143抑制了骨肉瘤细胞的增殖和转移。lncRNA CCAT2被确定为骨肉瘤治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/463e/7882883/e2fd611b8475/ol-21-04-12526-g00.jpg

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