Hsa-miR-10a-5p downregulation in mutant UQCRB-expressing cells promotes the cholesterol biosynthesis pathway

被引:11
作者
Kim, Jeong Eun [1 ]
Hong, Ji Won [1 ]
Lee, Hannah S. [1 ]
Kim, Wankyu [3 ]
Lim, Jisun [4 ]
Cho, Yoon Shin [4 ]
Kwon, Ho Jeong [1 ,2 ]
机构
[1] Yonsei Univ, Chem Genom Global Res Lab, Dept Biotechnol, Coll Life Sci & Biotechnol, Seoul 120749, South Korea
[2] Yonsei Univ, Dept Internal Med, Coll Med, Seoul 120752, South Korea
[3] Ewha Womans Univ, Ewha Res Ctr Syst Biol, Div Mol & Life Sci, Seoul, South Korea
[4] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
基金
新加坡国家研究基金会;
关键词
COA REDUCTASE INHIBITORS; MITOCHONDRIAL ACTIVITY; BINDING-PROTEIN; COMPLEX-III; CANCER; ANGIOGENESIS; ACTIVATION; MICRORNAS;
D O I
10.1038/s41598-018-30530-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ubiquinol cytochrome c reductase binding protein (UQCRB) is known to play crucial roles in the development of various types of diseases. However, the link between UQCRB and microRNAs remains unknown. In the present study, we performed microRNA sequencing of mutant UQCRB-expressing stable cell lines that exhibited pro-oncogenic activities caused by expression of the mutant UQCRB gene. Results showed that hsa-miR-10a-5p was significantly downregulated in the mutant UQCRB-expressing cell lines. Furthermore, mRNA sequencing and gene ontology analysis of differentially expressed genes (DEGs) revealed that the cholesterol biosynthesis pathway might be activation by mutant UQCRB expression. Moreover, inhibition of cholesterol synthesis in mutant UQCRB-expressing cells via treatment with the specific inhibitors suppressed the cell proliferation. Transfection with a hsa-miR-10a-5p mimic validated that lanosterol synthase (LSS) is a target of hsa-miR-10a-5p. In addition, hsa-miR-10a-5p was found to be downregulated in liver cancer cell lines overexpressing UQCRB. Taken together, our findings highlighted the potential use of hsa-miR-10a-5p as a biomarker for UQCRB related diseases.
引用
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页数:10
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