MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells.

INTRODUCTION: Thyroid cancer (TC) is a common endocrine malignancy, comprising nearly one-third of all head and neck malignancies worldwide. MicroRNAs (miRNAs) have been implicated in the malignant progression of multiple cancers; however, their contribution to thyroid diseases has not been fully explored. MATERIAL AND METHODS: This study aimed to illustrate the regulatory mechanism of microRNA-196a-5p in TC progression and to investigate whether microRNA-196a-5p affects progression of TC cells by targeting low-density lipoprotein receptor-associated protein 1B (LRP1B). MicroRNA-196a-5p and LRP1B expression status in TC cells and normal human thyroid cells was detected by quantative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay, cell counting kit-8 (CCK-8) assay, scratch healing assay, and Transwell assay were also performed. RESULTS: The results showed that microRNA-196a-5p expression was up-regulated and LRP1B expression was down regulated in TC cells. In addition, the upregulation of microRNA-196a-5p facilitated progression of TC cells. Silencing microRNA-196a-5p led to the opposite results. Dual-luciferase reporter assay offered evidence for microRNA-196a-5p targeting LRP1B in TC. MicroRNA-196a-5p could target LRP1B to facilitate proliferation, invasion, and migration of TC cells. CONCLUSION: Overall, this study revealed that microRNA-196a-5p may be a cancer-promoting microRNA that plays an important role in TC progression.

Constructing a thyroid cancer prognostic risk model based on CD8+ T cell associated genes.

Thyroid cancer (TC) is a common and curable endocrine tumor occurring in the head and neck characterized by a low mortality rate compared to other malignancies. In this study, the immune microenvironment of TC was investigated to identify biomarkers. The mRNA and clinical data available in this study were accessed from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) dataset. Differences in immune infiltration levels of TC and normal samples were assessed by CIBERSORT. Thyroid cancer samples were classified into high- and low-abundance groups according to the median abundance of immune cell infiltration, and CD8+ T cells were notably correlated with the survival status. Differential expression analysis was conducted on CD8+ T cells to obtain immune-related differentially expressed genes (DEGs). Subsequently, a prognostic risk model was established through Cox regression analysis. According to the median risk score, samples in the training set and validation set were assigned to high- and low-risk groups. The survival and ROC curves demonstrated that the model possesses favorable prognostic prediction ability. Furthermore, the results of gene set enrichment analysis (GSEA) indicated differences between the high- and low-risk groups in terms of ECM receptor interaction and transforming growth factor ß (TGF-ß) signaling pathways. The tumor microenvironment of TC samples was evaluated by ESTIMATE, which showed that stromal scores were higher in the high-risk group. Finally, simple-sample GSEA (ssGSEA) was performed on TC samples. The results indicated a higher infiltration level of NK cells in the low-risk group, as well as a lower level in the high-risk group. In terms of immune function-related gene sets, genes related to APC co-inhibition, cytolytic activity, HLA and T cell co-inhibition were observed to present higher expression levels in the low-risk group. In general, this study built a 6-gene prognostic risk assessment model based on CD8+ T cells through bioinformatics analysis, which is expected to be a reference for clinicians to judge the prognosis of TC patients.

Construction and Evaluation of a Tumor Mutation Burden-Related Prognostic Signature for Thyroid Carcinoma.

Thyroid carcinoma is a type of prevalent cancer. Its prognostic evaluation depends on clinicopathological features. However, such conventional methods are deficient. Based on mRNA, single nucleotide variants (SNV), and clinical information of thyroid carcinoma from The Cancer Genome Atlas (TCGA) database, this study statistically analyzed mutational signature of patients with this disease. Missense mutation and SNV are the most common variant classification and variant type, respectively. Next, tumor mutation burden (TMB) of sample was calculated. Survival status of high/low TMB groups was analyzed, as well as the relationship between TMB and clinicopathological features. Results revealed that patients with high TMB had poor survival status, and TMB was related to several clinicopathological features. Through analysis on DEGs in high/low TMB groups, 381 DEGs were obtained. They were found to be mainly enriched in muscle tissue development through enrichment analysis. Then, through Cox regression analysis, a 5-gene prognostic signature was established, which was then evaluated through survival curves and receiver operation characteristic (ROC) curves. The result showed that the signature was able to effectively predict patient's prognosis and to serve as an independent prognostic risk factor. Finally, through Gene Set Enrichment Analysis (GSEA) on high/low-risk groups, DEGs were found to be mainly enriched in signaling pathways related to DNA repair. Overall, based on the TCGA-THCA dataset, we constructed a 5-gene prognostic signature through a trail of bioinformatics analysis.

MiR-222-3p promotes the proliferation, migration and invasion of papillary thyroid carcinoma cells through targeting SLC4A4.

OBJECTIVE: An increasing number of studies indicate that miR-222-3p is upregulated in various cancers and can regulate tumor progression. This study aimed to explore the regulatory mechanism of miR-222-3p in papillary thyroid carcinoma (PTC). METHODS: TCGA database was used to dig differentially expressed miRNAs and mRNAs in PTC tissue. Relevant references were searched to determine target miRNA. StarBase, TargetScan and miRDB were applied to predict mRNAs that had binding sites with the target miRNA. Then, the mRNAs were intersected with differentially downregulated mRNAs in TCGA to determine the target mRNA. qRT-PCR was exerted to evaluate gene expression of miR-222-3p and SLC4A4 in PTC. Western blot was performed out to evaluate the protein expression of SLC4A4 in PTC cells. CCK-8, wound healing assay and cell invasion assay were undertaken to observe the proliferative, migratory, and invasive abilities of PTC cells. Dual-luciferase assay was employed to test the binding relationship between miR-222-3p and SLC4A4. RESULTS: MiR-222-3p was highly expressed in PTC while SLC4A4 was lowly expressed. Moreover, miR-222-3p was able to promote the proliferation, invasion, and migration of PTC cells. SLC4A4 was able to reverse these promotive effects of miR-222-3p. CONCLUSION: MiR-222-3p can promote the proliferation, migration and invasion of PTC cells through targeting SLC4A4. MiR-222-3p is expected to be a molecular therapeutic target for PTC patients.