Dataset Information

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation.

ABSTRACT: T helper 17 (Th17) cells protect against fungal and bacterial infections and are implicated in autoimmunity. Several long intergenic noncoding RNAs (lincRNA) are induced during Th17 differentiation, however, their contribution to Th17 differentiation is poorly understood. We aimed to characterize the function of the lincRNA Myocardial Infarction Associated Transcript (MIAT) during early human Th17 cell differentiation. We found MIAT to be upregulated early after induction of human Th17 cell differentiation along with an increase in the chromatin accessibility at the gene locus. STAT3, a key regulator of Th17 differentiation, directly bound to the MIAT promoter and induced its expression during the early stages of Th17 cell differentiation. MIAT resides in the nucleus and regulates the expression of several key Th17 genes, including IL17A, IL17F, CCR6 and CXCL13, possibly by altering the chromatin accessibility of key loci, including IL17A locus. Further, MIAT regulates the expression of protein kinase C alpha (PKCα), an upstream regulator of IL17A. A reanalysis of published single-cell RNA-seq data showed that MIAT was expressed in T cells from the synovium of RA patients. Our results demonstrate that MIAT contributes to human Th17 differentiation by upregulating several genes implicated in Th17 differentiation. High MIAT expression in T cells of RA patient synovia suggests a possible role of MIAT in Th17 mediated autoimmune pathologies.

SUBMITTER: Khan MM

PROVIDER: S-EPMC9242727 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation.

Khan Mohd Moin MM Khan Meraj Hasan MH Kalim Ubaid Ullah UU Khan Sofia S Junttila Sini S Paulin Niklas N Kong Lingjia L Rasool Omid O Elo Laura L LL Lahesmaa Riitta R

Frontiers in immunology 20220615

T helper 17 (Th17) cells protect against fungal and bacterial infections and are implicated in autoimmunity. Several long intergenic noncoding RNAs (lincRNA) are induced during Th17 differentiation, however, their contribution to Th17 differentiation is poorly understood. We aimed to characterize the function of the lincRNA Myocardial Infarction Associated Transcript (MIAT) during early human Th17 cell differentiation. We found MIAT to be upregulated early after induction of human Th17 cell diff ...[more]

PMID: 35784351

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Project description:The genotyping of long non-coding RNA (lncRNA)-related single-nucleotide polymorphisms (SNPs) could be associated with cancer risk and/or progression. This study aimed to analyze the angiogenesis-related lncRNAs MALAT1 (rs3200401) and MIAT (rs1061540) variants in patients with ovarian cancer (OC) using "Real-Time allelic discrimination polymerase chain reaction" in 182 formalin-fixed paraffin-embedded (FFPE) samples of benign, borderline, and primary malignant ovarian tissues. Differences in the genotype frequencies between low-grade ovarian epithelial tumors (benign/borderline) and malignant tumors and between high-grade malignant epithelial tumors and malignant epithelial tumors other than high-grade serous carcinomas were compared. Odds ratios (ORs)/95% confidence intervals were calculated as measures of the association strength. Additionally, associations of the genotypes with the available pathological data were analyzed. The heterozygosity of MALAT1 rs3200401 was the most common genotype (47.8%), followed by C/C (36.3%). Comparing the study groups, no significant differences were observed regarding this variant. In contrast, the malignant epithelial tumors had a higher frequency of the MIAT rs1061540 C/C genotype compared to the low-grade epithelial tumor cohorts (56.7% vs. 37.6, p = 0.031). The same genotype was significantly higher in high-grade serous carcinoma than its counterparts (69.4% vs. 43.8%, p = 0.038). Multivariate Cox regression analysis showed that the age at diagnosis was significantly associated with the risk of OC development. In contrast, the MIAT T/T genotype was associated with a low risk of malignant epithelial tumors under the homozygote comparison model (OR = 0.37 (0.16-0.83), p = 0.017). Also, MIAT T allele carriers were less likely to develop high-grade serous carcinoma under heterozygote (CT vs. CC; OR = 0.33 (0.12-0.88), p = 0.027) and homozygote (TT vs. CC; OR = 0.26 (0.07-0.90), p = 0.034) comparison models. In conclusion, our data provide novel evidence for a potential association between the lncRNA MIAT rs1061540 and the malignant condition of ovarian cancer, suggesting the involvement of such lncRNAs in OC development.

Dataset Information

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation.

Publications

Long Intergenic Noncoding RNA MIAT as a Regulator of Human Th17 Cell Differentiation.

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