測定在線蟲中NME4同源基因ndk-1是否受到let-7微小核糖核酸調控

Abstract

粒線體融合和分裂現象的不平衡參與調控癌症生成，Non-Metastatic 4 (NME4)是位在粒線體的核苷酸二磷酸激酶，其主要參與在粒線體融合的過程中。有趣的是，我們先前的結果顯示在人類細胞中，腫瘤抑制子let-7 miRNA可能調控NME4，使我們想尋找let-7 miRNA與粒線體的關聯性以及其生理上的意義。由於以線蟲研究let-7的功能和表型有許多優點，本篇研究使用線蟲作為模式生物，測定線蟲中NME4同源基因ndk-1是否會受到let-7調控。而我們也確實發現在線蟲中降低ndk-1基因表現會像在人類細胞中降低NME4一樣造成粒線體碎片化，且在mid L4階段的let-7(n2853)線蟲中，碎片化粒線體的比例也顯著下降，我們的實驗結果指出let-7可能影響粒線體型態，而我們的研究也是第一個嘗試探討let-7和粒線體型態功能上的關聯性，這有助於發現新的miRNA對於調控粒線體動態平衡的路徑。

Imbalance of mitochondrial fission and fusion activities has been implicated in carcinogenesis. NME4, a mitochondria-localized nucleoside diphosphate kinase, is involved in mitochondrial fusion process. Interestingly, our previous results showed that the tumor suppressor miRNA let-7 seems to regulate NME4 in human cells, inspiring us to seek possible functional connection for let-7 miRNA to mitochondrial and the biological implication for this connection. In this study, we chose C. elegans as the model organism due to its advantages in studying let-7 function and phenotypes. We seek to determine whether the NME4 homolog ndk-1 in C. elegans is also regulated by let-7. Indeed, like NME4 in human cells, knockdown of ndk-1 in C. elegans caused mitochondrial fragmentation. In addition, we found that fragmentation of mitochondria is significantly reduced in let-7(n2853) mutants at the mid L4 stage. These results suggest that let-7 may play a role in mitochondrial morphology. Our study is the first attempt to examine function relevance of let-7 to mitochondria morphology and will help discover novel pathways for miRNAs to control mitochondrial dynamics.