miR-372 and miR-373 enhance the stemness of colorectal cancer cells by repressing differentiation signaling pathways

Molecular Oncology
Lu-Qin WangLiang-Hu Qu

Abstract

miR-372/373, a cluster of stem cell-specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR-372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR-372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24-positive cell population and promoting self-renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA-induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR-372/373 and found that stemness-related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation-related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR-372/373. Numerous new targets of miR-372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR-372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA ...Continue Reading

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Citations

Jul 7, 2020·Cell Biochemistry and Function·Jia-Hui GuoFeng-Hou Gao
Jan 7, 2020·Molecular Cancer·Yizuo SongXueqiong Zhu
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Apr 27, 2021·Pharmacology & Therapeutics·Li ChenHaibo Xu
Sep 23, 2021·Biotechnology and Applied Biochemistry·Sahand MoazzendizajiHamed Mohammadi

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Methods Mentioned

BETA
fluorescence
transfection
transfections
electrophoresis
fluorescence activated cell sorting
PCR
Assay
FACS
xenograft
ubiquitination

Software Mentioned

gel analyzer
starbase
targetscan
Cignal

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