PDF(Pubmed)
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.
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.
摘要：
背景：这项计算分析研究了TRIM33基因和人类非编码（nc）RNA之间的序列互补性，并表征了它们在副肿瘤性皮肌炎背景下的相互作用。
方法：将TRIM33FASTA序列（NCBI参考序列：NC_000001.11）用于Ensembl.org数据库中针对人类GRCh38的BLASTN分析。在GeneCards.org数据库中搜索显示TRIM33命中的检索到的ncRNAs，并通过RNAInter进行进一步分析。QmRLFS-finder,Spliceator,和NcPath富集分析。
结果：共发现100个命中，涉及lncRNAsNNT-AS1，MKLN1-AS，LINC01206和PAXBP1-AS1，其失调已在癌症或皮肌炎中报道。此外,lncRNAsNNT-AS1和PAXBP1-AS1可能与microRNA-142-3p相互作用，降低其表达并增加TRIM33的表达。序列互补性仅影响TRIM33内含子1，可能导致TIF1γ的选择性剪接同种型，免疫原性增加。结果还揭示了TRIM33与参与免疫途径的28个ncRNA基因的基因调控元件之间的核苷酸比对。
结论：这项关键研究证明了TRIM33和在癌症和皮肌炎中失调的人ncRNAs之间的序列互补性。这种情况可能导致肿瘤中更多免疫原性TIF1γ变体的过度产生和自身免疫的刺激。需要使用靶向方法如Western印迹或Chip-Seq的进一步实验分析来确认这些数据。
方法：将TRIM33FASTA序列（NCBI参考序列：NC_000001.11）用于Ensembl.org数据库中针对人类GRCh38的BLASTN分析。在GeneCards.org数据库中搜索显示TRIM33命中的检索到的ncRNAs，并通过RNAInter进行进一步分析。QmRLFS-finder,Spliceator,和NcPath富集分析。
结果：共发现100个命中，涉及lncRNAsNNT-AS1，MKLN1-AS，LINC01206和PAXBP1-AS1，其失调已在癌症或皮肌炎中报道。此外,lncRNAsNNT-AS1和PAXBP1-AS1可能与microRNA-142-3p相互作用，降低其表达并增加TRIM33的表达。序列互补性仅影响TRIM33内含子1，可能导致TIF1γ的选择性剪接同种型，免疫原性增加。结果还揭示了TRIM33与参与免疫途径的28个ncRNA基因的基因调控元件之间的核苷酸比对。
结论：这项关键研究证明了TRIM33和在癌症和皮肌炎中失调的人ncRNAs之间的序列互补性。这种情况可能导致肿瘤中更多免疫原性TIF1γ变体的过度产生和自身免疫的刺激。需要使用靶向方法如Western印迹或Chip-Seq的进一步实验分析来确认这些数据。
