MiR-4435 is an UQCRB-related circulating miRNA in human colorectal cancer

Ji Won Hong, Jung Min Kim, Jeong Eun Kim, Hee Cho, Dasol Kim, Wankyu Kim, Jong Won Oh, Ho Jeong Kwon

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish
Article number2833
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
This work was partly supported by grants from the National Research Foundation of Korea, which is funded by the Korean government (MSIP-2012M3A9D1054520, 2015K1A1A2028365, 2016K2A9A1A03904900), and from the Brain Korea 21 Plus Project and ICONS(Institute of Convergence Science), Yonsei University.

Publisher Copyright:
© 2020, The Author(s).


Dive into the research topics of 'MiR-4435 is an UQCRB-related circulating miRNA in human colorectal cancer'. Together they form a unique fingerprint.

Cite this