Lnc-SELPLG-2:1 通过 hsa-miR-10a-5p 和 BTRC 级联促进骨肉瘤发生。

Lnc-SELPLG-2:1 enhanced osteosarcoma oncogenesis via hsa-miR-10a-5p and the BTRC cascade.

机构信息

Department of Spinal Surgery, the First People's Hospital of Foshan, North Lingnan Avenue 81, Foshan, 528000, Guangdong, China.

出版信息

BMC Cancer. 2022 Oct 5;22(1):1044. doi: 10.1186/s12885-022-10040-5.

DOI:10.1186/s12885-022-10040-5

PMID:36199080

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9533553/

Abstract

BACKGROUND

To investigate the potential role of Long Non-coding RNAs (lncRNAs) in the progression of osteosarcoma.

METHODS

The candidate lncRNAs were screened with RNA-seq and confirmed with quantitative real-time PCR. Using MTS, transwell assay, and flow cytometric analysis, the effects of overexpressed lnc-SELPLG-2:1 on cell functions were determined. Immunohistochemical staining, fluorescence in situ hybridization, and luciferase reporter assay were used to evaluate the potential mechanism of lnc-SELPLG-2:1 in vivo and in vitro using a tumor model. Moreover, the effects of overexpression of hsa-miR-10a-5p on the functions of SaOS2 cells were determined using functional cell analysis. A response test was used to confirm the mechanism by which lnc-SELPLG-2:1 sponge hsa-miR-10a-5p promotes the expression of BTRC to regulate osteosarcoma.

RESULTS

Lnc-SELPLG-2:1 was highly expressed in osteosarcoma compared to normal cells and bone and marrow samples. Inhibition of lnc-SELPLG-2:1 accelerated cell apoptosis and suppressed cell proliferation, migration, and invasion, whereas lnc-SELPLG-2:1 overexpression had the opposite effect. Moreover, inhibiting lnc-SELPLG-2:1 in an in vivo model decreased tumor size and suppressed the expression of cell migration-related proteins. The prediction, dual luciferase assay, and response test results indicated that hsa-miR-10-5p and BTRC were involved in the lnc-SELPLG-2:1 cascade. Unlike lnc-SELPLG-2:1, hsa-hsa-miR-10a-5p had opposite expression and function. Competitive binding of lnc-SELPLG-2:1 to hsa-hsa-miR-10a-5p prevented BTRC from miRNA-mediated degradation, thereby activating the expression of VIM, MMP9, and MMP2, promoting osteosarcoma cell proliferation, migration, and invasion, and inhibiting apoptosis.

CONCLUSION

Lnc-SELPLG-2:1 is an oncogenesis activator in osteosarcoma, and its functions are performed via hsa-miR-10a-5p /BTRC cascade.

摘要

背景

研究长链非编码 RNA（lncRNAs）在骨肉瘤进展中的潜在作用。

方法

使用 RNA-seq 筛选候选 lncRNAs，并使用定量实时 PCR 进行验证。通过 MTS、transwell 分析和流式细胞术分析，确定过表达 lnc-SELPLG-2：1 对细胞功能的影响。使用肿瘤模型，通过免疫组织化学染色、荧光原位杂交和荧光素酶报告基因分析，评估 lnc-SELPLG-2：1 在体内和体外的潜在机制。此外，通过功能细胞分析确定过表达 hsa-miR-10a-5p 对 SaOS2 细胞功能的影响。通过响应测试证实 lnc-SELPLG-2：1 海绵吸附 hsa-miR-10a-5p 促进 BTRC 表达以调节骨肉瘤的机制。

结果

与正常细胞和骨及骨髓样本相比，lnc-SELPLG-2：1 在骨肉瘤中高表达。抑制 lnc-SELPLG-2：1 可加速细胞凋亡，抑制细胞增殖、迁移和侵袭，而过表达 lnc-SELPLG-2：1 则有相反的效果。此外，在体内模型中抑制 lnc-SELPLG-2：1 可减小肿瘤体积并抑制细胞迁移相关蛋白的表达。预测、双荧光素酶测定和响应测试结果表明，hsa-miR-10-5p 和 BTRC 参与了 lnc-SELPLG-2：1 级联反应。与 lnc-SELPLG-2：1 不同，hsa-hsa-miR-10a-5p 的表达和功能相反。lnc-SELPLG-2：1 竞争性结合 hsa-hsa-miR-10a-5p 可防止 BTRC 被 miRNA 介导降解，从而激活 VIM、MMP9 和 MMP2 的表达，促进骨肉瘤细胞增殖、迁移和侵袭，并抑制凋亡。