Iron Status, Thyroid Dysfunction, and Iron Deficiency Anemia: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aimed to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction. METHODS: A two-sample mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based genome-wide association study databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK Biobank). Inverse variance-weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. RESULTS: The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.048-1.157, p < 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035, p < 0.001). Sensitivity analysis supported that the MR estimates were robust. CONCLUSION: In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.

LncRNA NCK1-AS1 Aggravates Hepatocellular Carcinoma by the miR-22-3p/YARS Axis to Activate PI3K/AKT Signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is frequently diagnosed at late stages when curative treatments are no more appliable. Many studies have proved the active role of long non-coding RNAs (lncRNAs) in cancers' biology; here, the functional role of lncRNA NCK1-AS1 in HCC was identified. METHODS: Gene expression in tumor tissues of HCC was evaluated by examining online databases and 88 collected HCC samples from our hospital. The interactions of miR-22-3p with NCK1-AS1 and tyrosyl-tRNA synthetase (YARS) were tested by conducting bioinformatics analysis, luciferase report, and RNA pulldown experiments. CCK-8, colony formation, flow cytometry, wound healing, transwell experiments were used to dissect the role of the NCK1-AS1/miR-22-3p/YARS axis in HCC. RESULTS: NCK1-AS1 was overexpressed in HCC cells and tissues. Functional assays depicted that depletion of NCK1-AS1 hampered malignant character of HCC cells. NCK1-AS1 controlled the availability of miR-22-3p, resulting in YARS upregulation. YARS was found to have a clinical value for HCC diagnosis. Moreover, rescue experiments revealed that miR-22-3p inhibition or YARS overexpression partially blocked the function of NCK1-AS1 deficiency in HCC cells. As for the downstream signaling pathway, we discovered that NCK1-AS1 activated PI3K/AKT signaling by the miR-22-3p/YARS axis. CONCLUSION: The present study verified that NCK1-AS1 could promote HCC progression via the miR-22-3p/YARS axis to activate PI3K/AKT signaling.

Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin ß1.

Schizophrenia is one of the most severe chronic psychiatric disorders, which lacks of objective and effective diagnosis and observation indicators.In this work, the serum miRNA profiles of schizophrenic patients were analyzed. Targets of abnormal miRNAs, and their regulatory mechanisms were studied. A miRNA array was used to analyze the serum from 3 schizophrenic patients without treatment, 3 clinically cured patients and 3 healthy controls. The findings from the array were confirmed by real-time PCR in a larger cohort, including 59 patients and 60 healthy controls. The candidate miRNAs were analyzed using bioinformatics tools. Their potential targets were studied through in vitro cellular experiments.MiR-320a-3p and miR-320b were found to be down-regulated in patients compared with cured patients and controls in the miRNA array, which was also confirmed by real-time PCR in the larger cohort. Integrin ß1 (ITG ß1) was found to be one of the targets of miR-320a-3p. An enzyme-linked immune sorbent assay demonstrated that the ITG ß1 concentration increased significantly in the patients' serum, and the in vitro study confirmed that miR-320a-3p targeted the 3' UTR of ITG ß1 mRNA and reduced its expression.Our results demonstrated that the regulatory effect of miR-320a-3p on its target ITG ß1 might play an important role in schizophrenia pathogenesis, which could be a potential pathway for schizophrenia diagnosis and therapy.