| Title: |
miR-132-3p regulates antibody-mediated complement-dependent cytotoxicity in colon cancer cells by directly targeting CD55. |
| Authors: |
Fan, Yu1 (AUTHOR), Liao, Juan1 (AUTHOR), Wang, Yu1 (AUTHOR), Wang, Zhu1 (AUTHOR), Zheng, Hong1 (AUTHOR), Wang, Yanping1 (AUTHOR) wyanping@scu.edu.cn |
| Source: |
Clinical & Experimental Immunology. Jan2023, Vol. 211 Issue 1, p57-67. 11p. 1 Diagram, 1 Chart, 4 Graphs. |
| Subject Terms: |
*CD55 antigen, *COLON cancer, *CANCER cells, *GENE expression, *ECULIZUMAB, *DRUG efficacy |
| Company/Entity: |
CENTERS for Disease Control & Prevention (U.S.) |
| Abstract: |
The overexpression of membrane-bound complement regulatory proteins (mCRPs) on tumour cells helps them survive complement attacks by suppressing antibody-mediated complement-dependent cytotoxicity (CDC). Consequently, mCRP overexpression limits monoclonal antibody drug immune efficacy. CD55, an mCRP, plays an important role in inhibiting antibody-mediated CDC. However, the mechanisms regulating CD55 expression in tumour cells remain unclear. Here, the aim was to explore CD55-targeting miRNAs. We previously constructed an in vitro model comprising cancer cell lines expressing α-gal and serum containing natural antibodies against α-gal and complement. This was used to simulate antibody-mediated CDC in colon cancer cells. We screened microRNAs that directly target CD55 using LoVo and Ls-174T colon cell lines, which express CD55 at low and high levels, respectively. miR-132-3p expression was dramatically lower in Ls-174T cells than in LoVo cells. miR-132-3p overexpression or inhibition transcriptionally regulated CD55 expression by specifically targeting its mRNA 3ʹ-untranslated regions. Further, miR-132-3p modulation regulated colon cancer cell sensitivity to antibody-mediated CDC through C5a release and C5b-9 deposition. Moreover, miR-132-3p expression was significantly reduced, whereas CD55 expression was increased, in colon cancer tissues compared to levels in adjacent normal tissues. CD55 protein levels were negatively correlated with miR-132-3p expression in colon cancer tissues. Our results indicate that miR-132-3p regulates colon cancer cell sensitivity to antibody-mediated CDC by directly targeting CD55. In addition, incubating the LoVo human tumour cell line, stably transfected with the xenoantigen α-gal, with human serum containing natural antibodies comprises a stable and cheap in vitro model to explore the mechanisms underlying antibody-mediated CDC. miR-132-3p regulates CD55 expression by directly targeting the 3ʹ-UTR of CD55, leading to changes in cell sensitivity to Ab-mediated CDC through the release of C5a and deposition of C5b-9. [ABSTRACT FROM AUTHOR] |
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| Database: |
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