HLA‐G 3′ untranslated region polymorphic sites associated with increased HLA‐G production are more frequent in patients exhibiting differentiated thyroid tumours

Abstract

HLA-G 3'UTR polymorphisms associated with a greater magnitude of HLA-G production were associated with differentiated thyroid tumours and with variables implicated in poor prognosis. These findings corroborate the unfavourable role of HLA-G in thyroid cancer.

HLA-G 3′ untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer

“…Interestingly, +3142G is suggested to increase the binding of miR-148a, miR-148b, and miR-152, suggesting that the allelic variation +3142C found in our cohort of patients might be disadvantageous by impairing binding of regulatory miRs regulatory control in the HLA-G 3′UTR. This is also in line with recent studies, in which the +3142CC genotype was shown to be associated with increased HLA-G levels and susceptibility to cancer 23,52 . Further, it already has been shown that some miRs bind to non-polymorphic sequences of the HLA-G 3′UTR in a stable and specific manner, while others bind to polymorphic sequences.…”

“…Our comparative haplotype analysis between healthy controls and EOC patients revealed that the overall frequencies of both cohorts are very similar to the ones found in worldwide population studies 25,26,32 . A study of haplotype distribution between papillary thyroid cancer and healthy controls demonstrated significant differences 23 . As we did not observe such differences in HLA-G 3′UTR distribution, this may point to distinct contribution of HLA-G genotypes to the onset of specific forms of cancer or oncological phenotypes.…”

“…Hitherto, the most studied SNP of the HLA-G 3′UTR are a 14 bp INS/DEL and +3142G/C. Although not consistent, the majority of studies have associated the14bp DEL as well as +3142C with high HLA-G production potentially promoting an immune-suppressive environment in various malignancies 23,45–47 . Importantly, the sHLA-G levels of the EOC patients in our study were significantly increased independent of the HLA-G 3′UTR haplotype implying that the tumor burden is the main source for the systemic release of sHLA-G molecules.…”

“…Importantly, the regulation of HLA-G expression and of its soluble forms encompasses post-transcriptional processes among which alternative splicing, altered mRNA stability, microRNA-mediated protein expression and impaired protein transport to the cell surface 2 . Especially the polymorphic 3′untranslated region (UTR) shared by the HLA-G1 to HLA-G6 transcripts (~370 bp) plays a pivotal role in HLA-G expression by interfering with transcription, splicing, mRNA stability and translation 23 . Here, sixteen single nucleotide polymorphisms (SNP; +3001C/T, +3003C/T, +3010C/G, +3027C/A, +3032C/G, +3035C/T, +3052C/T, +3092G/T, +3111A/G, +3121C/T, +3142C/G, +3177G/T, +3183A/G, +3187A/G, +3196C/G, and +3227A/G) and a 14 bp insertion/deletion (INS/DEL) located at position +2961 have been identified in the 3′UTR potentially modifying the affinity of gene targeted sequences for post-transcriptional factors 24 .…”

Identification of RNA Expression Profiles in Thyroid Cancer to Construct a Competing Endogenous RNA (ceRNA) Network of mRNAs, Long Noncoding RNAs (lncRNAs), and microRNAs (miRNAs)

“…Luo et al demonstrated that overexpression of the CHI3L1 gene was significantly associated with tumor metastasis and reduced OS in patients with thyroid cancer [17]. Also, CLDN10, E2F1, and HLA-G gene expression have been previously reported to be associated with poor survival in thyroid cancer [18–20], which are findings that support those of the present study.…”