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The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.

ABSTRACT: Papillary thyroid carcinoma (PTC), a common thyroid cancer (TC) subtype, rapidly increases in occurrence. MicroRNAs (miRNAs), which are non-coding small RNAs, have been demonstrated to play a role in cancer pathogenic mechanisms. Although miR-143 is involved in suppressing certain malignant tumor progression, its biological role is unknown in PTC. The present study found that miR-143 levels were strongly lower in PTC patient samples and cell lines, implying that miR-143 may play a biological role in PTC. Down-regulation of miR-143 resulted in the increased expression of HMGA2. Furthermore, HMGA2 was found to be a direct target of miR-143. A dual-luciferase assay confirmed a direct binding site for miR-143 was confirmed on HMGA2 using a dual-luciferase assay. Next, over-expression of miR-143 suppressed PTC cell growth as analyzed by MTT, clone formation, and Ki-67 immunofluorescence staining assays. miR-143 mimics transfection downregulated the expression of PCNA, CDK4, CDK1, and Cyclin E1. In addition, wound healing and trans-well assays revealed that miR-143 up-regulation inhibited PTC cells invasion and migration. Co-transfection of HMGA2 expression vector restored HMGA2 expression and rescued PTC cells proliferation capability in miR-143 mimics transfected PTC cells, indicating that miR-143 inhibited PTC cells proliferation via HMGA2. These observations were also obtained in xenografts experiments in nude mice. Altogether, our study shed light on miR-143's anti-cancer biological functions in PTC progression through targeting HMGA2, suggesting that restoration of miR-143 could be a potential therapeutic approach for PTC treatment.

SUBMITTER: Ding C

PROVIDER: S-EPMC8973723 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.

Ding Chao C Shi Tiefeng T Wu Gang G Man Jianting J Han Hongyu H Cui Yunfu Y

Bioengineered 20220301 3

Papillary thyroid carcinoma (PTC), a common thyroid cancer (TC) subtype, rapidly increases in occurrence. MicroRNAs (miRNAs), which are non-coding small RNAs, have been demonstrated to play a role in cancer pathogenic mechanisms. Although miR-143 is involved in suppressing certain malignant tumor progression, its biological role is unknown in PTC. The present study found that miR-143 levels were strongly lower in PTC patient samples and cell lines, implying that miR-143 may play a biological rol ...[more]

PMID: 35213273

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Project description:The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA-genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value?<?0.05; log2 fold change???-1.0 or ?1.0) in PTC LNM-P and PTC LNN compared to adjacent normal tissues, respectively. Ninety-six miRNAs had significant expression ratios of 3p-to-5p in PTC LNM-P as compared to PTC LNN. In addition, ribosomal RNA-reduced RNA sequencing analysis revealed 699 significantly deregulated genes in PTC LNM-P versus normal adjacent tissues, 1,362 genes in PTC LNN versus normal adjacent tissue, and 1,576 genes in PTC LNM-P versus PTC LNN. We provide the evidence of miRNA and gene interactions, which are involved in LNM of papillary thyroid cancer. These findings may lead to better understanding of carcinogenesis and metastasis processes. This study also complements the existing knowledge about deregulated miRNAs in papillary thyroid carcinoma development.

Dataset Information

The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.

Publications

The anti-cancer role of microRNA-143 in papillary thyroid carcinoma by targeting high mobility group AT-hook 2.

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