环状 RNA BBS9 通过海绵吸附 miR-485-3p/HMGB1 轴加速骨肉瘤的恶性进展。

CircBBS9 accelerates the malignant progression of osteosarcoma through sponging miR-485-3p/HMGB1 axis.

机构信息

Department of Orthopaedics, Beijing Daxing District People's Hospital-Capital Medical University Daxing Teaching Hospital, Beijing, 102600, China.

出版信息

J Orthop Sci. 2024 Jul;29(4):1130-1139. doi: 10.1016/j.jos.2023.05.005. Epub 2023 May 27.

DOI:10.1016/j.jos.2023.05.005

PMID:37248151

Abstract

BACKGROUND

Osteosarcoma (OS) is a leading malignant tumor reported with high mortality and morbidity. Dysexpression of CircBBS9 has been reported to exhibit a critical functional role in various diseases. However, the underlying molecular mechanisms of CircBBS9 in osteosarcoma are poorly characterized.

METHODS

The present study aims to investigate the impacts of CircBBS9 on the progression of osteosarcoma.

RESULTS

The findings of the study demonstrated the up-regulated expression of CircBBS9 in osteosarcoma. The Actinomycin D and RNase R treatment experiments confirmed that circBBS9 is indeed a circRNA. In addition, the knockdown of circBBS9 negatively impacted the migration, proliferation and invasion of osteosarcoma cells. Further investigations illustrated that circBBS9 controlled miR-485-3p and miR-485-3p might directly interact with HMGB1. miR-485-3p had a negative regulatory role in HMGB1's gene expression. Through rescue assays, it was verified that CircBBS9 promoted osteosarcoma progression through the miR-485-3p/HMGB1 axis. Finally, circBBS9 knockdown attenuated the in-vivo growth of osteosarcoma.

CONCLUSIONS

Conclusively, our study is the first time to examine the possible functional mechanism and regulation roles of CircBBS9 in osteosarcoma. The findings explained that CircBBS9 promoted the malignant osteosarcoma's progression by sponging miR-485-3p/HMGB1 and proposed CircBBS9 as a prognostic biomarker and therapeutic candidate for osteosarcoma patients.

摘要

背景

骨肉瘤（OS）是一种死亡率和发病率都很高的主要恶性肿瘤。CircBBS9 的异常表达已被报道在各种疾病中发挥关键的功能作用。然而，CircBBS9 在骨肉瘤中的潜在分子机制仍知之甚少。

方法

本研究旨在探讨 CircBBS9 对骨肉瘤进展的影响。

结果

研究结果表明 CircBBS9 在骨肉瘤中呈上调表达。放线菌素 D 和 RNase R 处理实验证实 circBBS9 确实是一种 circRNA。此外，circBBS9 的敲低显著抑制骨肉瘤细胞的迁移、增殖和侵袭。进一步研究表明，circBBS9 调控 miR-485-3p，而 miR-485-3p 可能直接与 HMGB1 相互作用。miR-485-3p 对 HMGB1 的基因表达起负调控作用。通过挽救实验证实，CircBBS9 通过 miR-485-3p/HMGB1 轴促进骨肉瘤的进展。最后，circBBS9 的敲低减弱了骨肉瘤的体内生长。