Increased TRIM31 gene expression is positively correlated with SARS-CoV-2 associated genes TMPRSS2 and TMPRSS4 in gastrointestinal cancers

Abstract

Besides typical respiratory symptoms, COVID-19 patients also have gastrointestinal symptoms. Studies focusing on the gastrointestinal tumors derived from gastrointestinal tissues have raised a question whether these tumors might express higher levels of SARS-CoV-2 associated genes and therefore patients diagnosed with GI cancers may be more susceptible to the infection. In this study, we have analyzed the expression of SARS-CoV-2 associated genes and their co-expressions in gastrointestinal solid tumors, cancer cell lines and patient-derived organoids relative to their normal counterparts. Moreover, we have found increased co-expression of TMPRSS2-TMPRSS4 in gastrointestinal cancers suggesting that SARS-CoV-2 viral infection known to be mediated by this protease pair might facilitate the effects of viral infection in GI cancer patients. Further, our findings also demonstrate that TRIM31 expression is upregulated in gastrointestinal tumors, while the inhibition of TRIM31 significantly altered viral replication and viral processes associated with cellular pathways in gastrointestinal cancer samples. Taken together, these findings indicate that in addition to the co-expression of TMPRSS2-TMPRSS4 protease pair in GI cancers, TRIM31 expression is positively correlated with this pair and TRIM31 may play a role in providing an increased susceptibility in GI cancer patients to be infected with SARS-CoV-2 virus.

Pan-Cancer Analysis of the COVID-19 Causal Gene SLC6A20

“…Rapid increase in the SARS-CoV-2 infection rates worldwide resulted in an immediate response to understand the underlying mechanisms of the COVID-19 disease, including in cancer patients. Cancer patients are considered as more prone to develop COVID-19 especially because of the impaired immune system response seen in them against the SARS-CoV-2 vaccine. , Studies demonstrated that ACE2, TMPRSS2, and TMPRSS4 expression were upregulated and facilitated SARS-CoV-2 infection in tumor samples. , In addition, certain host-specific genetic factors have been shown to play a critical role in increased susceptibility to COVID-19 in cancer patients . One of the causal genes identified to be linked with COVID-19 severity was SLC6A20 gene located in the chromosome 3p21.31; , however, its link with pan-cancer tumor samples remained to be elucidated.…”

“…Cancer is a complex inflammatory disease and linked to an impaired immune system. − Several studies have shown that cancer patients can be more susceptible to SARS-CoV-2 infection than the general population. , Although in-depth understanding of the susceptibility of cancer patients to COVID-19 is still unclear, COVID-19-associated genes, ACE2, TMPRSS2, and TMPRSS4 were upregulated and co-expressed in different cancer types. − In addition to pan-cancer studies, COVID-19 susceptibility in cancer patients was explained with elevated levels of endosomal entry and recycling proteins for SARS-CoV-2 infection . Given the accumulating evidence documenting COVID-19 susceptibility in cancer patients, characterizing additional genes in these patients could contribute to identifying new targets.…”

SCAT8/miR-125b-5p axis triggers malignant progression of nasopharyngeal carcinoma through SCARB1

“…Both lncRNAs and miRNAs are involved in the inflammatory cascade of scavenger receptors and subsequent regulation of the lipid metabolism pathways [ 36 ]. The expression of SCARB1 in gastric cancer tissues is significantly down-regulated, and its mechanism of action may be associated with the post-transcriptional regulation of SCARB1 mRNA by miRNA [ 7 , 29 ]. For example, during tumor occurrence, high levels of miR-199 can bind to the 3' UTR of the SCARB1 mRNA, thus inhibiting the expression of SCARB1 [ 13 , 38 , 45 , 46 ].…”

TRIM31: A molecule with a dual role in cancer

“…also found that TRIM31 is positively correlated with SARS−CoV−2 associated genes TMPRSS2−TMPRSS4 and knockdown of TRIM31 significantly altered viral replication and viral processes in gastrointestinal cancer samples. This result suggests that TRIM31 may play a role in increasing the susceptibility to SARS-CoV-2 viral infection in patients with gastrointestinal cancers ( 66 ).…”