Abstract
Ubiquinol-cytochrome c reductase (UQCRB), a subunit of the mitochondrial complex III, is highly expressed in tissues from colorectal cancer patients. Since UQCRB is highly expressed in colorectal cancer, we investigated miRNAs from mutant UQCRB-expressing cell lines to identify new miRNA biomarkers. After sequencing miRNAs in the mutant UQCRB-expressing cell lines, miR-4435 was selected as a potential biomarker candidate from the six up-regulated miRNAs. The expression level of miR-4435 in the mutant UQCRB-expressing cell lines and colon cancer was increased. Notably, the expression level of miR-4435 was increased in exosomes isolated from cell culture medium, suggesting that miR-4435 is closely related to colon cancer and that large amounts of miR-4435 may be secreted outside of the cells through exosomes. Additionally, exosomes extracted from the serum samples of colorectal cancer patients showed increased miR-4435 levels depending on the cancer progression stage. Moreover, analyses of a miRNA database and mRNA-sequencing data of the mutant UQCRB-expressing cell lines revealed that TIMP3, a tumor suppressor, could be a target of miR-4435. Additionally, the expression of miR-4435 was suppressed by UQCRB inhibitor treatment whereas TIMP3 was up-regulated. Upregulation of TIMP3 decreased proliferation of the mutant UQCRB-expressing cell lines and a colorectal cancer cell line. TIMP3 was also upregulated in response to miR-4435 inhibitor and UQCRB inhibitor treatments. Furthermore, these findings suggest that miR-4435 is related to an oncogenic function in UQCRB related disease, CRC, and that effects migration and invasion on mutant UQCRB-expressing cell lines and colorectal cancer cell. In conclusion, our results identified miR-4435 as a potential circulating miRNA biomarker of colorectal cancer associated with UQCRB.
Highlights
Ubiquinol-cytochrome c reductase (UQCRB), a subunit of the mitochondrial complex III, is highly expressed in tissues from colorectal cancer patients
We validated whether miR-4435 level was upregulated in mutant Ubiquinol-cytochrome c reductase binding protein (UQCRB)-expressing cell lines compared to the control cell line (HEK293) by quantitative RT-PCR
These results demonstrated that miR-4435 was up-regulated in mutant UQCRB-expressing cell lines and colon cancer cells
Summary
Ubiquinol-cytochrome c reductase (UQCRB), a subunit of the mitochondrial complex III, is highly expressed in tissues from colorectal cancer patients. TIMP3 was upregulated in response to miR-4435 inhibitor and UQCRB inhibitor treatments These findings suggest that miR-4435 is related to an oncogenic function in UQCRB related disease, CRC, and that effects migration and invasion on mutant UQCRB-expressing cell lines and colorectal cancer cell. The downregulation of miR-10a-5p activates the cholesterol pathway in mutant UQCRB-expressing cells by targeting the cholesterol-synthesizing enzyme, suggesting a possible role of miRNA related with UQCRB in the proliferation of cancer cells[21]. These miRNAs are stable in serum and plasma and their expression levels vary under different disease conditions, such as cancer[22]. The mechanism and regulation of these miRNAs in disease is still not clear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
