TYK2 single-nucleotide variants associated with the severity of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is a lethal disease caused by the coronavirus SARS-CoV-2, which can result in a broad clinical spectrum of respiratory symptoms. While many clinical risk factors such as concomitant chronic diseases play roles in the pathophysiology of COVID-19, genetic predisposition factors have not been widely studied. The aim of this study was, therefore, to evaluate the relationship between some singlenucleotide polymorphisms (SNPs) of the human genes TYK2 and ACE2 and the severity of SARS-CoV-2 infection. Genomic DNA was isolated from 200 SARS-CoV-2-infected individuals with severe (n = 100) or mild (n = 100) disease. Owing to the importance of ACE2 and TYK2 genes in regulating the immune response to SARS-CoV-2 infection, TYK2 gene SNPs, i.e. rs2304255, rs2304256, rs12720270, and rs12720354 and ACE2 rs382746 variants, were genotyped in the samples. To confirm the results, the expression of different TYK2 genotypes was investigated using real-time PCR. The presence of the nucleotide T at the locus rs2304255 was shown to be a risk factor linked to disease severity (OR [95% CI] = 3.2485 [2.1554-4.8961]). Similarly, the presence of A at the locus rs12720354 increased the risk of severity (OR [95% CI]) = 3.9721 [2.6075-6.0509]). In contrast, the presence of A at the loci rs2304256 and rs12720270 was observed to reduce the severity risk (OR [95% CI] = 0.2495 [0.1642-0.3793] and 0.1668 [0.1083-0.2569], respectively). Real-time PCR results also demonstrated that the expression level of TYK2 in samples with the TT genotype of rs2304255 and the AA genotype of rs12720354 and in samples with the GG genotype of rs12720207 was significantly lower than in those with other genotypes. The results of this study suggest that TYK2 SNPs might be utilized to identify individuals who are at risk for severe COVID-19, in order to better manage their health care. It is predicted that the presence of some alleles (T in rs2304255, A in rs12720354, and G in rs12720207) of TYK2 can affect COVID-19 severity by reducing TYK2 expression and thereby affecting the regulatory role of TYK2 in the immune response.

ESRG, LINC00518 and PWRN1 are newly-identified deregulated lncRNAs in colorectal cancer.

Colorectal cancer is the 2nd leading cause of death in humans because of cancer. This rank of death could be due to the high rate of incidence from one hand, and the lack of sufficient diagnostic and therapeutic approaches from the other hand. Thus, molecular tools have been emerging as the potential biomarker to improve the early diagnosis and therapeutic management that subsequently could lead to the heightened survival rate of colorectal cancer patients. Long non-coding RNA (lncRNAs) have shown promising capabilities to be used in clinics. The profiling methods could identify novel aberrantly expressed lncRNAs in colorectal cancer. We, thus, performed a comprehensive and unbiased approach to shortlist the dysregulated lncRNAs based on the colon adenocarcinoma TCGA data. An unbiased in silico method was used to rank the yet to profiled lncRNAs in colorectal cancer. qPCR was used to measure the expression level of selected lncRNAs. Our results nominated ESRG, LINC00518, PWRN1, and TTTY14 lncRNAs as the top-hit novel lncRNAs with aberrant expression in colon cancer. The qPCR method was used to profile these lncRNAs that showed the up-regulation of ESRG and LINC00518, and down-regulation of TTTY14 in thirty paired colorectal cancer specimens. The statistical analyses demonstrated that ESRG, LINC00518 and PWRN1 could distinguish the tumor from normal samples. Moreover, ESRG showed a negative correlation with the overall survival of patients. These diagnostic and prognostic results suggest that profiling ESRG, LINC00518 and PWRN1 s may have implications in clinics.