Publication:
Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer

dc.contributor.authorGiordo, Roberta
dc.contributor.authorLipovich, Leonard
dc.date.accessioned2023-08-17T04:12:07Z
dc.date.available2023-08-17T04:12:07Z
dc.date.issued2023
dc.description.abstractIntroduction: 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.other204-2023.56
dc.identifier.urihttps://repository.mbru.ac.ae/handle/1/1285
dc.language.isoenen_US
dc.subjectBreast Canceren_US
dc.subjectMitochondriaen_US
dc.subjectAutoimmunityen_US
dc.subjectLong Non-coding RNAen_US
dc.subjectCarcinogenesisen_US
dc.subjectPhage Displayen_US
dc.titleNon-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast canceren_US
dc.typeArticleen_US
dspace.entity.typePublicationen_US

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