The hsa-miR-3613-5p, a potential oncogene correlated with diagnostic and prognostic merits in kidney renal clear cell carcinoma.

MicroRNA-3613 (hsa-miR-3613-5p), a biomarker with a dual role as an oncogenic or tumor suppressor, is associated with different types of cancer. This study aimed to determine the correlation between the hsa-miR-3613-5p gene expression and Kidney renal clear cell carcinoma (KIRC). Utilizing several bioinformatics tools, we examined the expression level and clinicopathological value of hsa-miR-3613-5p in patients with KIRC compared to normal tissues. Other bioinformatic measures, including survival analysis, diagnostic merit of hsa-miR-3613-5p, downstream target prediction, potential upstream lncRNAs, network construction, and functional enrichment analysis of hsa-miR-3613-5p, were performed. We observed that overexpression of hsa-miR-3613-5p in KIRC tissues had valuable diagnostic merit and was significantly correlated with the poor overall survival of KIRC patients. We also realized a correlation between abnormal expression of hsa-miR-3613-5p and several clinical parameters such as pathological stage, race, age, and histological grades in patients with KIRC. Moreover, we constructed the most potential regulatory network of hsa-miR-3613-5p in KIRC with 17 different axes, including four pseudogenes, two lncRNAs, and three mRNAs. Besides, we uncovered six variants in the mature form of hsa-miR-3613-5p. Finally, pathway enrichment analysis demonstrated that the top-ranked pathways for hsa-miR-3613-5p are cell cycle, cell adhesion molecules (CAMs), and hepatocellular carcinoma pathways. The present report suggests that the higher expression of hsa-miR-3613-5p is associated with the progression of KIRC. Therefore, it may be considered a valuable indicator for the early detection, risk stratification, and targeted treatment of patients with KIRC.

Contribution of HLA class II genes, DRB4*01:01, DRB1*07:01, and DQB1*03:03:2 to clinical features of Vitiligo disease in Iranian population.

BACKGROUND: Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. Increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests a crucial role for the participation of immune response in Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population. METHODS: First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through the salting-out method. Then, HLA class II genotyping was performed using the sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes was evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula. RESULTS: Our results indicated the positive associations of DRB4*01:01 and DRB1*07:01 allelic genes with early-onset Vitiligo (p = 0.024 and 0.022, respectively). DRB4*01:01 also showed strong protection against late-onset Vitiligo (p = 0.0016, RR = 0.360). Moreover, our data revealed that the DRB1*07:01 increases the susceptibility to Sporadic Vitiligo (p = 0.030, RR = 1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB4*01:01 and DRB1*07:01 alleles maybe is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor. CONCLUSION: Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo should also be considered.

Inhibition of c-Myc using 10058-F4 induces anti-tumor effects in ovarian cancer cells via regulation of FOXO target genes.

Ovarian cancer, characterized by rapid growth and asymptomatic development in the early stage, is the fifth common cancer in women. The deregulated expression of c-Myc in more than 50% of human tumors including ovarian cancer makes this oncogenic master transcription factor a potential therapeutic target for cancer treatment. In the present study, we evaluated the anti-tumor effects of 10058-F4, a small molecule c-Myc inhibitor, on ovarian cancer cells. We found that 10058-F4 not only inhibited the proliferation and clonal growth of ovarian cancer cells but also enhanced the cytotoxic effects of chemotherapeutic drugs. Our results also revealed that c-Myc inhibition using 10058-F4 increased the intracellular reactive oxygen species production coupled with suppressed expression of hTERT. RT-qPCR analysis indicated that 10058-F4 enhanced the mRNA levels of the forkhead box O (FOXO) family of transcription factors, including FOXO1, 3, and 4. Moreover, 10058-F4 induced G1 cell cycle arrest in 2008C13 ovarian cancer cells, along with increased expression of some key targets of FOXOs involved in the regulation of cell cycle such as p15, p21, p27, and GADD45A. The results of our study also showed that the 10058-F4-induced apoptosis in 2008C13 cell line was associated with the upregulation of FOXO downstream genes, including PUMA, Bim, and FasL. In conclusion, our results, for the first time, suggest that the anti-tumor effects of 10058-F4 in ovarian cancer cells might be mediated through upregulation of FOXO transcription factors and their key target genes involved in G1 cell cycle arrest, apoptosis, and autophagic cell death.