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

Jeong Eun Kim, Ji Won Hong, Hannah S. Lee, Wankyu Kim, Jisun Lim, Yoon Shin Cho, Ho Jeong Kwon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Article number12407
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - 1 Dec 2018

Bibliographical note

Funding Information:
We are grateful for helpful discussions and experimental help from Dr. Sung Wook Yang, Yonsei University. This work was supported by grants from the National Research Foundation of Korea, which funded by the Korean government (MSIP-2012M3A9D1054520, 2015K1A1A2028365) and from the Brain Korea 21 Plus Project.

Publisher Copyright:
© 2018, The Author(s).

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