Let-7a通过靶向线粒体编码的ND4诱导乳腺癌细胞发生代谢重编程。
Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4.
作者信息
Sharma Praveen, Sharma Vibhuti, Ahluwalia Tarunveer Singh, Dogra Nilambra, Kumar Santosh, Singh Sandeep
机构信息
Molecular Medicine Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, India.
Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh, India.
出版信息
Cancer Cell Int. 2021 Nov 27;21(1):629. doi: 10.1186/s12935-021-02339-3.
BACKGROUND AND OBJECTIVES
MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria.
METHODS AND RESULTS
Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells.
CONCLUSION
These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.
背景与目的
从细胞核转运至线粒体的微小RNA（miRNA）被称为线粒体微小RNA（mitomiR）。尽管已证明mitomiR可调节基因表达，但其在线粒体内的功能影响尚不清楚。本研究的主要目的是调查线粒体基因组是否受线粒体内存在的miR调控。
方法与结果
在此，我们报告mitomiR let-7a调节乳腺癌细胞中的线粒体转录并相应地重塑代谢。如通过RNA下拉实验所研究的，这些效应是通过let-7a与线粒体DNA（mtDNA）的相互作用介导的，以细胞系特异性方式改变复合体I的活性。我们的研究首次确定了mitomiR（let-7a）通过转录抑制调节线粒体基因组的作用及其对调节乳腺癌细胞线粒体代谢的贡献。
结论
这些发现揭示了mitomiR调节线粒体转录的新机制。
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