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MicroRNA-183-3p is a predictor of worsening heart failure in adult patients with transposition of the great arteries and a systemic right ventricle

ABSTRACT: AIM: MicroRNAs (miRNAs) have been shown to play an important role in the progression of heart failure (HF). The aim of our study was to analyze miRNAs in the blood of patients with transposition of the great arteries and a systemic right ventricle (TGA-RV) in order to identify those that predict worsening HF. MATERIALS AND METHODS: In 36 patients with TGA-RV, SurePrint™ 8×60K Human v21 miRNA arrays were used to determine the miRNA abundance profiles and compared to 35 age- and gender-matched healthy volunteers (HVs). MiRNAs that were most significantly abundant or best related to worsening HF were further validated by RT-qPCR. RESULTS: Using miRNA array analysis, a total of 50 down-regulated and 56 up-regulated miRNAs were found to be differentially abundant in TGA-RV patients compared to HVs. 6 of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, 4 miRNAs turned out to be significantly associated with worsening HF, namely miR-150-5p, miR-1255b-5p, miR-423-3p, and miR-183-3p. In the stepwise multivariable Cox regression analysis, ejection fraction of the systemic RV and miR-183-3p were found to be independent predictors of worsening HF (P<0.001 and P=0.008, respectively). CONCLUSIONS: In patients with TGA-RV, miR-183-3p is an independent predictor of worsening HF and thus may be used as additional biomarker in the risk assessment of these patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179105 | GEO | 2021/09/29

REPOSITORIES: GEO

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Project description:Background: Laryngeal squamous cell carcinoma (LSCC) is the most common type in head and neck squamous cell carcinoma (HNSCC), and the development of LSCC are multistep processes accompanied by changes of molecular biology. Objective: The purpose of this study was to investigate the miRNAs basis of tumorigenesis in LSCC, and analyze the microRNAs dysregulation related with the six targeted genes (CDK1,CDK2, CDK4, MCM2, MCM3, MCM4) which were related to tumorigenesis from the screened miRNAs. Methods: A total number of 5 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for miRNA array analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by the Affymetrix GeneChip miRNA Array 3.0 to screen effective miRNAs, then mirfocus 3.0 database (http://mirfocus.org/index.php) was adopted to select putative regulated miRNAs of the six targeted genes. Moreover, the selected putative regulated miRNAs were also validated by qRT-PCR in another 36 patients diagnosed for LSCC. Results: Analysed by the miRNAs arrays, there were 127 miRNAs significantly related to tumorigenesis ,and 78 showed a higher expression in tumor than in non-tumor tissue while 49 presented the contrasting pattern(P<0.01).Then analyzed by mirfocus 3.0 database, there were 2 putative regulated miRNAs, hsa-miR-24-3p and hsa-miR-183-5p, corresponding to three of the six targeted genes. Among the 2 putative miRNAs, hsa-miR-24-3p regulated MCM4,CDK1 and CDK4,while hsa-miR-183-5p regulated MCM4 only. Another miRNA we should focus on is hsa-miR-30a-5p, a tumor-suppressive factor, which was down-expressed obviously analysed by the miRNAs arrays. The expression of the 3 putative regulated miRNAs were also validated by qRT-PCR in another 36 patients (P<0.05). Conclusions: The research revealed 127 miRNAs expression signature of tumorigenesis in laryngeal squamous cell carcinoma,and analyzed 3 putative regulated miRNAs, hsa-miR-24-3p, hsa-miR-183-5p and hsa-miR-30a-5p, as potential diagnostic and therapeutic markers in LSCC. The result will contribute to the understanding of the molecular basis of LSCC and help to improve the treatment.

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MicroRNA-183-3p is a predictor of worsening heart failure in adult patients with transposition of the great arteries and a systemic right ventricle

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