TYMSOS-微小RNA-101-3p-NETO2轴促进骨肉瘤进展。

TYMSOS-miR-101-3p-NETO2 axis promotes osteosarcoma progression.

作者信息

Zhang Zun, Wang Jin, Zhang Xiaoyan, Ran Bo, Wen Jie, Zhang Hong

机构信息

Orthopaedic Dapartment, Inner Mongolia Baogang Hospital (Third Affiliated Hospital of Inner Mongolia Medical University), No.20 of shaoxian Road, Kundulun District, Baotou, 014010, China.

Neurology Dapartment, Inner Mongolia Baogang Hospital (Third Affiliated Hospital of Inner Mongolia Medical University), No.20 of shaoxian Road, Kundulun District, Baotou, 014010, China.

出版信息

Mol Cell Probes. 2023 Feb;67:101887. doi: 10.1016/j.mcp.2022.101887. Epub 2022 Dec 9.

DOI:10.1016/j.mcp.2022.101887

PMID:36509232

Abstract

BACKGROUND

Osteosarcoma (OS) is a type of bone cancer most often affects pre-teens and teens, but it is still a rare disorder. Neuropilin and tolloid-like 2 (NETO2) has been reported to promote OS progression, but its upstream mechanism in OS cells remains obscure.

METHODS

Quantitative real-time PCR (RT-qPCR) and Western blot were conducted to examine RNA and protein levels, separately. Functional assays were performed to assess the impact of NETO2 on OS cell malignancy. Moreover, bioinformatics analyses and mechanism experiments were performed to identify the upstream mechanism of NETO2 in OS cells.

RESULTS

Functionally, NETO2 depletion repressed cell proliferation, migration and invasion as well as epithelial-mesenchymal transition (EMT) but triggered the apoptosis of OS cells. NETO2 is directly targeted and negatively regulated by microRNA-101-3p (miR-101-3p). Mechanically, miR-101-3p could combine with long noncoding RNA (lncRNA) TYMS opposite strand RNA (TYMSOS) in OS cells. In addition, our study proved that TYMSOS promotes the malignancy of OS via elevating NETO2 expression as miR-101-3p sponge.

CONCLUSION

TYMSOS-miR-101-3p-NETO2 axis promotes the malignant behaviors of OS cells, which might offer a novel sight for OS treatment.

摘要

背景

骨肉瘤（OS）是一种骨癌，最常影响青少年，但它仍然是一种罕见的疾病。据报道，神经纤毛蛋白和类 tolloid 样蛋白 2（NETO2）可促进骨肉瘤进展，但其在骨肉瘤细胞中的上游机制仍不清楚。

方法

分别进行定量实时 PCR（RT-qPCR）和蛋白质免疫印迹法检测 RNA 和蛋白质水平。进行功能实验以评估 NETO2 对骨肉瘤细胞恶性程度的影响。此外，进行生物信息学分析和机制实验以确定 NETO2 在骨肉瘤细胞中的上游机制。

结果

在功能上，NETO2 的缺失抑制了细胞增殖、迁移和侵袭以及上皮-间质转化（EMT），但引发了骨肉瘤细胞的凋亡。NETO2 是微小 RNA-101-3p（miR-101-3p）的直接靶点并受到其负调控。在机制上，miR-101-3p 可在骨肉瘤细胞中与长链非编码 RNA（lncRNA）胸苷酸合成酶反义链 RNA（TYMSOS）结合。此外，我们的研究证明，TYMSOS 作为 miR-101-3p 的海绵，通过提高 NETO2 的表达促进骨肉瘤的恶性程度。