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McKenna posted an update 1 year, 1 month ago
It has been revealed from microarray data analysis that long intergenic non‑coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription‑quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The ex an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.Thyroid hormones (TH) are multifunctional mediators that fine‑tune several physiological processes, including metabolic rate, digestive function and tissue development via interactions with type II nuclear thyroid hormone receptors (TR). selleck chemicals llc Upon binding of TH, TRs interact specifically with thyroid hormone response elements of target gene promoter regions to regulate their transcription. Earlier studies suggested a correlation between aberrant TR regulation and hepatocellular carcinoma (HCC). THs are involved in a crosstalk between hepatoma and stromal cells, and disruption of TH signaling is associated with tumorigenesis. Previous cDNA microarray analysis of target gene expression following T3 treatment of wild‑type TR‑expressing hepatoma cells led to the identification of forkhead box M1 (FOXM1) as a factor negatively regulated by T3 and associated with poor prognosis in several cancer types. Increased FOXM1 expression during late stages of HCC was associated with poorer overall and recurrence‑free survival in patients with HCC. However, the specific mechanisms underlying FOXM1 activity in liver cancer progression remain to be elucidated. Experiments from the present study showed that TH/TR signaling suppresses FOXM1 mRNA and protein expression. Depletion of FOXM1 induced inhibition of the cell growth rate and a decline in oncogenic cyclin D1, cyclin E and CDK2 expression. Conversely, overexpression of FOXM1 enhanced cell proliferation and expression of oncogenic factors, which was decreased upon FOXM1 depletion. Re‑expression of FOXM1 partially rescued suppression of cell proliferation induced by T3. Collectively, the present findings suggest that TH/TR participates in HCC progression via modulation of FOXM1 expression.Although primary open‑angle glaucoma (POAG)‑related mutations in the myocilin (MYOC) gene have been reported, the underlying associations remain poorly understood. In the present study, the relationship between a MYOC mutation and POAG was investigated using ophthalmic examination and total exon gene sequencing in a Chinese family comprised of 5 individuals with POAG and 15 unaffected individuals. Pathogenic mutations underlying POAG were identified by whole‑exome sequencing and subsequently validated by Sanger sequencing. Of the family members, nine (45%) harbored heterozygous p.D208Y mutations; among these, five had POAG and four were unaffected. The mean age at diagnosis was 26.2±4.12 years and the mean intraocular pressure (IOP) was 39.7±16.58 mmHg; all affected members complained of vision loss, headaches and eye swelling. Among the five cases of POAG, two presented with blindness. Among 10 members of the family who underwent comprehensive ophthalmologic examination, 3 individuals exhibited severe visual field defects. The mean age at the time of operation was 27.2±3.54 years. In the present study, a novel MYOC mutation (c.G622T p.D208Y) was identified that was associated with severe visual impairment, high IOP and the need for frequent surgical interventions. Some carriers of the mutation were young and did not show signs of glaucoma. These individuals should be followed‑up to firmly establish whether the mutated gene is pathogenic for POAG.Astrotactin 1 (ASTN1) is known to serve a physiological role in neuronal migration; however its role in liver cancer remains to be determined. In the present study, ASTN1 levels were lower in liver cancer tissues compared with those in matching normal tissue. ASTN1 levels were negatively associated with microscopic vascular invasion, advanced clinical stage and a less favorable prognosis in patients with hepatocellular carcinoma (HCC). Furthermore, ASTN1 overexpression in a liver cancer cell line reduced the migratory and invasive capacity of the cells. Based on bioinformatics analysis, ASTN1 levels were negatively associated with the Wnt signaling pathway. In addition, ASTN1 downregulated the protein expression levels of β‑catenin, T‑cell factor (TCF)1, TCF4, Jun proto‑oncogene (C‑jun), Myc proto‑oncogene (C‑myc), cyclooxygenase‑2 (COX2), metalloproteinase (MMP)2, MMP9 and vascular endothelial growth factor (VEGF) protein levels, indicative of suppression of Wnt signaling. Furthermore, XAV939‑induced Wnt signaling suppression reversed the ASTN1‑mediated inhibition of invasion and migration in cells. Overexpression of ASTN1 in xenografts reduced cancer development as well as Wnt signaling. TIMER analysis showed that ASTN1 expression was negatively correlated with B cell, macrophage and neutrophil infiltrating levels in HCC. Together, the results of the present study showed that ASTN1 reduced the migratory and invasive capacity of liver cancer cells, potentially served as a candidate biomarker for diagnosis and prediction of the prognosis of HCC, and was associated with immune infiltration. Understanding the underlying mechanisms of action of ASTN1 may facilitate the development of novel strategies for prevention and treatment of liver cancer.