NSUN6 Maintains BMPER Stability in an m5C-Dependent Manner to Suppress Cell Proliferation and Migration in Hepatocellular Carcinoma

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Chunlin Liu, Yumin Wu, Ying Wu, Weizhi Luo, Yuefei Hong, Leichang Jiang, Senrui Wang, Duanming Du
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引用次数: 0

Abstract

Background

The expression of Nop2/Sun domain family member 6 (NSUN6), an RNA m5C methyltransferase, is correlated with the prognosis of various cancers. However, its role in the progression of hepatocellular carcinoma (HCC) remains elusive.

Methods

The expression of NSUN6 was analyzed using the TCGA-HCC cohort, as well as through quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting in tumor tissues from HCC patients and various HCC cell lines. Moreover, its biological functions were detected using cell counting kit 8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell invasion assays in vitro, as well as in an HCC patient-derived xenograft (PDX) mouse model in vivo. The molecular mechanism underlying NSUN6 was explored using methylated RNA immunoprecipitation sequencing (MeRIP-seq), double luciferase reporter gene assay, actinomycin-D assay, and rescue experiments in SNU449 cell lines.

Results

The expression level of NSUN6 was significantly decreased in the TCGA-HCC cohort, tumor tissues of HCC patients and HCC cell lines. NSUN6 overexpression markedly inhibited the proliferative and migratory abilities of HCC cells in the PDX mouse model. Additionally, BMPER was identified as a downstream target of NSUN6, while NSUN6 could stabilize BMPER expression in an m5C-dependent manner. Finally, BMPER knockdown reversed the positive effects of NSUN6 in suppressing HCC progression.

Conclusion

This study elucidated the inhibitory effect of NSUN6 overexpression in HCC development, with BMPER identified as a downstream target of NSUN6. NSUN6 regulates BMPER expression in an m5C-dependent manner, thereby influencing HCC progression. Overall, these results suggest that the NSUN6/BMPER axis may serve as a potential therapeutic target for HCC.

Abstract Image

NSUN6以m5c依赖的方式维持BMPER稳定性,抑制肝细胞癌细胞增殖和迁移
Nop2/Sun结构域家族成员6 (NSUN6)是一种RNA m5C甲基转移酶,其表达与多种癌症的预后相关。然而,其在肝细胞癌(HCC)进展中的作用仍不明确。方法采用TCGA-HCC队列、实时定量逆转录聚合酶链反应(qRT-PCR)和western blotting技术,分析NSUN6在肝癌患者肿瘤组织和各种肝癌细胞系中的表达。此外,通过细胞计数试剂盒8 (CCK8)、菌落形成、5-乙基-2 ' -脱氧尿苷(EdU)、伤口愈合和跨井侵袭试验,以及体内肝癌患者来源的异种移植(PDX)小鼠模型,检测其生物学功能。通过甲基化RNA免疫沉淀测序(MeRIP-seq)、双荧光素酶报告基因测定、放放菌素- d测定和SNU449细胞系的拯救实验,探讨了NSUN6的分子机制。结果NSUN6在TCGA-HCC队列、HCC患者肿瘤组织和HCC细胞系中的表达水平显著降低。在PDX小鼠模型中,NSUN6过表达明显抑制HCC细胞的增殖和迁移能力。此外,BMPER被确定为NSUN6的下游靶点,而NSUN6可以以m505依赖的方式稳定BMPER的表达。最后,BMPER敲低逆转了NSUN6在抑制HCC进展方面的积极作用。结论本研究阐明了NSUN6过表达对HCC发展的抑制作用,并确定BMPER是NSUN6的下游靶点。NSUN6以m5c依赖的方式调节BMPER的表达,从而影响HCC的进展。总之,这些结果表明NSUN6/BMPER轴可能作为HCC的潜在治疗靶点。
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来源期刊
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
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