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LINC01140通过靶向miR-139-5p/HOXA9轴调控骨肉瘤的增殖和侵袭。

LINC01140 regulates osteosarcoma proliferation and invasion by targeting the miR-139-5p/HOXA9 axis.

作者信息

Zhang Shufang, Chen Rongchun

机构信息

The Spinal Surgery Department, People's Hospital of Ganzhou City, Jiangxi Province, PR China.

出版信息

Biochem Biophys Rep. 2022 Jun 28;31:101301. doi: 10.1016/j.bbrep.2022.101301. eCollection 2022 Sep.

DOI:10.1016/j.bbrep.2022.101301
PMID:35800618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9253409/
Abstract

Osteosarcoma is one of the commonest metastatic tumor in children and teenagers, and has a hopeless, prognosis. Long non-coding RNA (lncRNA) acts momentous roles as a regulator on the proliferation and migration of cancer. Here, we performed GEO database analysis and qPCR to identify differentially expressed lncRNAs in osteosarcoma cells. Knockdown of lncRNA LINC01140 was used to detect the effect of LINC01140 on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. Bioinformatics analysis and qPCR identified the LINC01140/miR-139-5p/Homeobox A9 (HOXA9) regulatory axis. RNA immunoprecipitation assay, Dual-luciferase assay, and rescue experiments confirmed the interaction of LINC01140/miR-139-5p/HOXA9 in osteosarcoma. LINC01140 was overexpressed in osteosarcoma and knocking down LINC01140 restrained the proliferation and invasion of osteosarcoma cells and EMT. In Saos2 and MG63 cells, LINC01140 sponged miR-139-5p, and a miR-139-5p inhibitor overturned the suppression of LINC01140 knockdown on the proliferation and migration of osteosarcoma cells. Moreover, miR-139-5p depressed the invasion, proliferation, and EMT of osteosarcoma cells via targeting HOXA9. Our results indicate that LINC01140 downregulation inhibits the invasion, proliferation, and EMT in osteosarcoma cells through targeting the miR-139-5p/HOXA9 axis. Therefore, LINC01140 is a potential therapeutic target for osteosarcoma.

摘要

骨肉瘤是儿童和青少年中最常见的转移性肿瘤之一,预后很差。长链非编码RNA(lncRNA)作为癌症增殖和迁移的调节因子发挥着重要作用。在此,我们进行了GEO数据库分析和qPCR,以鉴定骨肉瘤细胞中差异表达的lncRNA。通过敲低lncRNA LINC01140来检测其对骨肉瘤细胞增殖、侵袭和上皮-间质转化(EMT)的影响。生物信息学分析和qPCR确定了LINC01140/miR-139-5p/同源框A9(HOXA9)调控轴。RNA免疫沉淀实验、双荧光素酶实验和拯救实验证实了LINC01140/miR-139-5p/HOXA9在骨肉瘤中的相互作用。LINC01140在骨肉瘤中高表达,敲低LINC01140可抑制骨肉瘤细胞的增殖、侵袭和EMT。在Saos2和MG63细胞中,LINC01140吸附miR-139-5p,miR-139-5p抑制剂可逆转LINC01140敲低对骨肉瘤细胞增殖和迁移的抑制作用。此外,miR-139-5p通过靶向HOXA9抑制骨肉瘤细胞的侵袭、增殖和EMT。我们的结果表明,LINC01140的下调通过靶向miR-139-5p/HOXA9轴抑制骨肉瘤细胞的侵袭、增殖和EMT。因此,LINC01140是骨肉瘤潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/238f233afc27/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/f109dacbaa2b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/bd5a9dd84578/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/bbbcf3a6e353/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/922d64d306ca/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/dbdbc23187c5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/238f233afc27/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/f109dacbaa2b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/bd5a9dd84578/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/bbbcf3a6e353/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/922d64d306ca/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/dbdbc23187c5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea7/9253409/238f233afc27/gr6.jpg

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Genomic variants exclusively identified in children with birth defects and concurrent malignant tumors predispose to cancer development.仅在有出生缺陷和并发恶性肿瘤的儿童中发现的基因组变异可导致癌症发生。
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