RESUMO
Knowledge regarding the relationship between the molecular mechanisms underlying atherosclerosis (AS) and transfer RNA-derived small RNAs (tsRNAs) is limited. This study illustrated the expression profile of tsRNAs, thus exploring its roles in AS pathogenesis. Small RNA sequencing was performed with four atherosclerotic arterial and four healthy subject samples. Using bioinformatics, the protein-protein interaction network and cellular experiments were constructed to predict the enriched signalling pathways and regulatory roles of tsRNAs in AS. Of the total 315 tsRNAs identified to be dysregulated in the AS group, 131 and 184 were up-regulated and down-regulated, respectively. Interestingly, the pathway of the differentiated expression of tsRNAs in cell adhesion molecules (CAMs) was implicated to be closely associated with AS. Particularly, tRF-Gly-GCC might participate in AS pathogenesis via regulating cell adhesion, proliferation, migration and phenotypic transformation in HUVECs and VSMCs. In conclusion, tsRNAs might help understand the molecular mechanisms of AS better. tRF-Gly-GCC may be a promising target for suppressing abnormal vessels functions, suggesting a novel strategy for preventing the progression of atherosclerosis.
Assuntos
Aterosclerose/genética , Pequeno RNA não Traduzido/metabolismo , RNA de Transferência/metabolismo , Aterosclerose/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Pequeno RNA não Traduzido/genética , RNA de Transferência/genética , TranscriptomaRESUMO
Papillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan-Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC. Moreover, overexpression of miR-127 significantly enhanced cell proliferation, migration, and invasion of PTC by targeting REPIN1. miR-127 may be involved in the progression of PTC, which provides a new therapeutic strategy for PTC.
Assuntos
Proteínas de Ligação a DNA/genética , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Câncer Papilífero da Tireoide/genética , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/fisiopatologiaRESUMO
Ribosomal S6 kinase 4 (RSK4) is a putative tumor suppressor gene which is inactivated by epigenetic events in a number human malignancies; however, its role in papillary thyroid carcinoma (PTC) remains largely unknown. The aim of this study was to explore the methylation status of the RSK4 promoter in PTC, and to determine its potential role in thyroid carcinogenesis. Reverse transcriptionquantitative PCR (RTqPCR) and western blot analyses were performed to examine the RSK4 mRNA and protein levels, respectively. Methylationspecific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to analyze methylation status of the RSK4 gene. Sanger sequencing was further carried out to detect the BRAF V600E mutation. Cell proliferation assay was finally performed to evaluate the role of hypermethylation in the growth of PTC cells. The association between RSK4 methylation and the clinicopathological characteristics of patients with PTC was assessed. The methylation frequency of the RSK4 promoter in PTC tissues was higher than that in paired paracancerous tissues. Coincidentally, the RSK4 mRNA levels were also downregulated in PTC tissues when compared with the paracancerous counterparts. The hypermethylation of RSK4 was associated with tumor size and lymph node metastasis. Furthermore, the BRAF V600E mutation may influence RSK4 expression and methylation. Moreover, RSK4 hypermethylation was observed in thyroid cancer cell lines, which was consistent with a lack of RSK4 expression. Upon the 5Azadeoxycytidine treatment of thyroid cancer cells, RSK4 expression was significantly upregulated, while cell proliferation was inhibited. On the whole, the findings of the present study demonstrate that the hypermethylation of the RSK4 promoter may be one of the mechanisms responsible for the poor RSK4 expression in PTC. Thus, these data suggest that RSK4 may serve as a molecular target for the early diagnosis and treatment of PTC.