Affiliation:
1. Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital “Gaetano Martino”, 98124 Messina, Italy
Abstract
Background: This computational analysis investigated sequence complementarities between the TRIM33 gene and human noncoding (nc)RNAs and characterized their interactions in the context of paraneoplastic dermatomyositis. Methods: TRIM33 FASTA sequence (NCBI Reference Sequence: NC_000001.11) was used for BLASTN analysis against Human GRCh38 in the Ensembl.org database. Retrieved ncRNAs showing hits to TRIM33 were searched in the GeneCards.org database and further analyzed through RNAInter, QmRLFS-finder, Spliceator, and NcPath enrichment analysis. Results: A total of 100 hits were found, involving the lncRNAs NNT-AS1, MKLN1-AS, LINC01206, and PAXBP1-AS1, whose dysregulation has been reported in either cancer or dermatomyositis. Additionally, the lncRNAs NNT-AS1 and PAXBP1-AS1 may interact with microRNA-142-3p, reducing its expression and increasing that of TRIM33. Sequence complementarity affected only TRIM33 intron 1, possibly resulting in alternatively spliced isoforms of TIF1γ with increased immunogenicity. The results also revealed nucleotide alignment between TRIM33 and the gene regulatory elements of 28 ncRNA genes involved in immune pathways. Conclusions: This pivotal study demonstrates sequence complementarity between TRIM33 and human ncRNAs dysregulated in cancer and dermatomyositis. This scenario may lead to the overproduction of more immunogenic TIF1γ variants in tumors and the stimulation of autoimmunity. Further experimental analyses using targeted methods such as Western blot or Chip-Seq are required to confirm these data.