Publication: Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer
dc.contributor.author | Giordo, Roberta | |
dc.contributor.author | Lipovich, Leonard | |
dc.date.accessioned | 2023-08-17T04:12:07Z | |
dc.date.available | 2023-08-17T04:12:07Z | |
dc.date.issued | 2023 | |
dc.description.abstract | Introduction: Autoantibodies against mitochondrial-derived antigens play a key role in chronic tissue inflammation in autoimmune disorders and cancers. Here, we identify autoreactive nuclear genomic DNA (nDNA)-encoded mitochondrial gene products (GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH) recognized by breast cancer (BC) patients’ sera as nonself, supporting a direct relationship of mitochondrial autoimmunity to breast carcinogenesis. Autoreactivity of multiple nDNA-encoded mitochondrial gene products was mapped to protein-coding regions, 3’ untranslated regions (UTRs), as well as introns. In addition, autoantibodies in BC sera targeted intergenic sequences that may be parts of long non-coding RNA (lncRNA) genes, including LINC02381 and other putative lncRNA neighbors of the protein-coding genes ERCC4, CXCL13, SOX3, PCDH1, EDDM3B, and GRB2. Increasing evidence indicates that lncRNAs play a key role in carcinogenesis. Consistent with this, our findings suggest that lncRNAs, as well as mRNAs of nDNA-encoded mitochondrial genes, mechanistically contribute to BC progression. This work supports a new paradigm of breast carcinogenesis based on a globally dysfunctional genome with altered function of multiple mitochondrial and non-mitochondrial oncogenic pathways caused by the effects of autoreactivity-induced dysregulation of multiple genes and their products. This autoimmunity-based model of carcinogenesis will open novel avenues for BC treatment. | en_US |
dc.identifier.other | 204-2023.56 | |
dc.identifier.uri | https://repository.mbru.ac.ae/handle/1/1285 | |
dc.language.iso | en | en_US |
dc.subject | Breast Cancer | en_US |
dc.subject | Mitochondria | en_US |
dc.subject | Autoimmunity | en_US |
dc.subject | Long Non-coding RNA | en_US |
dc.subject | Carcinogenesis | en_US |
dc.subject | Phage Display | en_US |
dc.title | Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer | en_US |
dc.type | Article | en_US |
dspace.entity.type | Publication | en_US |