A m6A writer RBM15 enhances the cell malignancy of osteosarcoma by mediating m6A modification of lncRNA THAP9-AS1

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-02-25 DOI:10.1016/j.yexcr.2025.114490

Hao Zou , Fei Hu , Xin Wu , Bin Xu , Guifeng Shang , Dong An , Dehao Qin , Xiaolei Zhang , Aofei Yang

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引用次数: 0

Abstract

Background

Osteosarcoma (OS) remains a potentially fatal disease in children. Increasing evidence highlights the implication of lncRNAs and N6-methyladenosine (m6A) modification in OS malignancies. Here, we aimed to decipher the pathological significance of RBM15-mediated m6A modification of lncRNA THAP9-AS1 in OS progression.

Methods

The expression levels of THAP9-AS1 and RBM15 in OS tissues and cell lines was determined by qRT-PCR. Based on the abnormal regulation of THAP9-AS1 and RBM15, the CCK8, colony-formation, and transwell invasion assays were used to evaluate the viability, clone formation capacity, and invasive ability of OS cells. A mouse model of tumor transplantation was utilized to ascertain the role of THAP9-AS1 silencing in vivo. The relationship between THAP9-AS1 and RBM15 was determined by RIP and MeRIP assays.

Results

THAP9-AS1 and RBM15 were significantly elevated in OS. Silencing of THAP9-AS1 or RBM15 decreased the proliferative and invasive ability of OS cells in vitro, and inhibition of THAP9-AS1 delayed the tumorous growth in vivo. Interestingly, THAP9-AS1 binds to RBM15, and was stimulated by RBM15 to promote m6A level and translation. Furthermore, THAP9-AS1 upregulation promoted OS cell invasion and survival, and this promotion of OS cell malignancy was abrogated by RBM15 silencing.

Conclusion

THAP9-AS1 serves as a tumor promoter by accelerating the malignant progression of OS by undergoing m6A modification, which is mediated by RBM15. This suggests that RBM15-m6A-THAP9-AS1 may be a potential target for OS treatment.

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背景：骨肉瘤（Osteosarcoma，OS）仍然是儿童中一种潜在的致命疾病。越来越多的证据凸显了lncRNA和N6-甲基腺苷（m6A）修饰在骨肉瘤恶性肿瘤中的影响。在此，我们旨在解读RBM15介导的lncRNA THAP9-AS1的m6A修饰在OS进展中的病理意义：方法：通过qRT-PCR检测THAP9-AS1和RBM15在OS组织和细胞系中的表达水平。在THAP9-AS1和RBM15异常调控的基础上，采用CCK8、集落形成和Transwell侵袭试验评估OS细胞的活力、克隆形成能力和侵袭能力。为了确定THAP9-AS1沉默在体内的作用，研究人员利用了小鼠肿瘤移植模型。通过RIP和MeRIP检测确定了THAP9-AS1和RBM15之间的关系：结果：THAP9-AS1和RBM15在OS中明显升高。结果：THAP9-AS1和RBM15在OS中明显升高，沉默THAP9-AS1或RBM15可降低OS细胞在体外的增殖和侵袭能力，抑制THAP9-AS1可延缓肿瘤在体内的生长。有趣的是，THAP9-AS1 与 RBM15 结合，并受 RBM15 的刺激促进 m6A 水平和翻译。此外，THAP9-AS1的上调促进了OS细胞的侵袭和存活，而这种促进OS细胞恶性生长的作用在RBM15沉默后被减弱：结论：THAP9-AS1在RBM15的介导下，通过进行m6A修饰加速OS的恶性进展，从而成为肿瘤的促进因子。这表明RBM15-m6A-THAP9-AS1可能是治疗OS的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.