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.
Highlights
Mitochondrial dysfunction has been implicated to play a key role in various diseases, such as metabolic diseases and cancer[1,2,3,4,5]
Mutant Ubiquinol cytochrome c reductase binding protein (UQCRB)-expressing stable cell lines were subjected to miRNA sequencing to identify differentially expressed miRNAs that are specific to mutant UQCRB
Twelve key candidate miRNAs that were differentially expressed between the mutant UQCRB and human embryonic kidney cells 293 (HEK293) cell lines were selected based on the following criteria: |log2FC| > 1, log2CPM > 2, and false discovery rate (FDR) < 0.15
Summary
Mitochondrial dysfunction has been implicated to play a key role in various diseases, such as metabolic diseases and cancer[1,2,3,4,5]. Identification of a target protein of terpestacin, an anti-angiogenic natural product, revealed a new role of UQCRB in regulation of mitochondrial ROS (mROS) generation and angiogenesis[7]. Based on the above findings, our group generated mutant UQCRB-expressing stable cell lines, namely, MT1 and MT2, and investigated their angiogenic properties. The MT1 showed a higher expression level of mutant UQCRB protein than MT2 and both cell lines showed significantly faster cell growth and pro-angiogenic activities than those of control host human embryonic kidney cells 293 (HEK293). We performed microRNA and mRNA deep sequencing of mutant UQCRB-expressing stable cell lines with control host cell HEK293 to identify novel microRNA biomarkers for UQCRB related diseases
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