OPA1-Exon4b modulates the migration and invasion of hepatocellular carcinoma cells by ATP regulation

Haite Tang , Zhijuan Hu , Liang Yang , Zifeng Ruan , Hao Wang , Yunhao Zhou , Feixiang Bao , Xingguo Liu
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Abstract

Optic Atrophy 1 (OPA1), a mitochondrial inner protein, is involved in both mitochondrial fusion dynamic and cell apoptosis. OPA1 Exon4b (OPA1-Exon4b) was reported to be downregulated in hepatocellular carcinoma (HCC). However, the relationship between OPA1-Exon4b and HCC remains unclear. Here we demonstrated that OPA1-Exon4b is related with migration using genome-wide transcriptome profiling. OPA1-Exon4b overexpression suppresses the migration and invasion, and cellular ATP production in HCC cells. The inhibition of migration and invasion by OPA1-Exon4b overexpression could be rescued by ATP addition, showing that OPA1-Exon4b suppresses the migration and invasion by decreasing ATP. We further demonstrated OPA1 overexpression induces the enlargement of mtDNA nucleoids in HCC cells. Thus, our study demonstrated a key role of OPA1-Exon4b to regulate the migration and invasion in HCC, which could provide a new prospect for the clinical diagnosis and therapy of HCC.

OPA1-Exon4b通过ATP调节肝癌细胞的迁移和侵袭
视神经萎缩1(OPA1)是一种线粒体内部蛋白,参与线粒体融合动力学和细胞凋亡。据报道,OPA1-Exon4b在肝细胞癌(HCC)中被下调。然而,OPA1-Exon4b与HCC之间的关系尚不清楚。在这里,我们使用全基因组转录组分析证明了OPA1-Exon4b与迁移有关。OPA1-Exon4b过表达抑制HCC细胞的迁移和侵袭以及细胞ATP的产生。OPA1-Exon4b过表达对迁移和侵袭的抑制可以通过添加ATP来挽救,表明OPA1-Exon 4b通过降低ATP来抑制迁移和侵袭。我们进一步证明了OPA1过表达诱导HCC细胞中mtDNA类核的扩增。因此,我们的研究证明了OPA1-Exon4b在HCC中调节迁移和侵袭的关键作用,这可能为HCC的临床诊断和治疗提供新的前景。
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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