The severe acute respiratory syndrome coronavirus (SARS-CoV) was first emerged 17 years ago (Drosten et al., 2003). Later in December 2019 in Wuhan, China, a novel coronavirus (SARS-CoV-2) appeared and was found that it is able to infect humans (Gorbalenya et al., 2020) and lead to a pneumonia outbreak (Jiang et al., 2020). This virus causes coronavirus disease-19 (COVID-19) with mild to severe lung injury and multi-organ failure symptoms, eventually leading to death, especially in older patients with other comorbidities. However, genetic or environmental factors increasing the susceptibility to SARS-CoV-2 remained unclear.Angiotensin-converting enzyme 2 (ACE2; OMIM accession number = 300335) was identified as the functional SARS-CoV receptor in vitro and in vivo (Imai et al., 2005;

Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53 —a natural antisense transcript—regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5′ regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D′ for each combination of the markers were calculated via the Haploview program. Our results showed that the GA 1 CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA 1 CC and CA 2 GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA 1 GC haplotype was strongly identified as a breast cancer risk factor, and the GA 1 CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer.

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Background: The Notch signaling pathway has a key role in angiogenesis and Delta-Like Ligand 4 (DLL4) is one of the main ligands of Notch involved in cell proliferation in sprouting vessels. Objective: In this study, we aimed to evaluate the expression of DLL4 in primary breast tumors and to examine the effect of melatonin on DLL4 expression in vitro. Methods: Eighty-five breast tumor and paired adjacent non-tumor tissue samples were collected. Apoptosis assay was performed on breast cancer cells to evaluate melatonin effects. Western blot and quantitative RT-PCR were used to measure DLL4 expression. Then, we investigated the effect of melatonin on the expression of DLL4 in four breast cancer cell lines at RNA and protein levels. We also performed Probabilistic Neural Network analysis to study genes closely associated with DLL4 expression. Results: Our results showed a significantly higher expression of DLL4 in tumor tissues as compared to non-tumor tissues (P = 0.027). Melatonin treatment substantially attenuated DLL4 expression in BT474 and MCF-7 cells, but not in SK-BR3 and MDA-MB-231 cells. Also, melatonin induced apoptosis in all four cell lines. Network analysis revealed a set of 15 genes that had close association and interaction with DLL4. DLL4 was overexpressed in breast cancer tissues as compared to the non-tumor tissues. Conclusion: It can be concluded that melatonin treatment attenuated DLL4 expression only in estrogen-responsive breast cancer cells and is able to induce apoptosis in breast cancer cells.