Crosstalk between hypoxia-induced pyroptosis and immune escape in cancer: From mechanisms to therapy.

Pyroptosis can be triggered through both canonical and non-canonical inflammasome pathways, involving the cleavage of gasdermin (GSDM) protein family members, like GSDMD and GSDME. The impact of pyroptosis on tumors is nuanced, because its role in regulating cancer progression and anti-tumor immunity may vary depending on the tumor type, stage, location, and immune status. However, pyroptosis cannot be simply categorized as promoting or inhibiting tumors based solely on whether it is acute or chronic in nature. The interplay between pyroptosis and cancer is intricate, with some evidence suggesting that chronic pyroptosis may facilitate tumor growth, while the acute induction of pyroptosis could stimulate anti-cancer immune responses. Tumor hypoxia activates hypoxia inducible factor (HIF) signaling to modulate pyroptosis and immune checkpoint expression. Targeting this hypoxia-pyroptosis-immune escape axis could be a promising therapeutic strategy. This review highlights the complex crosstalk between hypoxia, pyroptosis, and immune evasion in the TME.

MicroRNA binding site polymorphism in inflammatory genes associated with colorectal cancer: literature review and bioinformatics analysis.

Inflammation, among environmental risk factors, is one of the most important contributors to colorectal cancer (CRC) development. In this way, studies revealed that the incidence of CRC in inflammatory bowel disease patients is up to 60% higher than the general population. MicroRNAs (miRNAs), small noncoding RNA molecules, have attracted excessive attention due to their fundamental role in various aspects of cellular biology, such as inflammation by binding to the 3'-untranslated regions (3'-UTR) of pro and anti-inflammatory genes. Based on multiple previous studies, SNPs at 3'-UTR can affect miRNA recognition elements by changing the thermodynamic features and secondary structure. This effect can be categorized, based on the number of changes, into four groups, including break, decrease, create, and enhance. In this paper, we will focus on functional variants in miRNA binding sites in inflammatory genes, which can modulate the risk of CRC by both investigating previous studies, regarding miRSNPs in inflammatory genes associated with CRC and recruiting in silico prediction algorithms to report putative miRSNPs in 176 inflammatory genes. In our analysis, we achieved 110 miRSNPs in 3'-UTR of 67 genes that seem good targets for future researches.

Novel mutations in mitochondrial carrier family gene SLC25A38, causing congenital sideroblastic anemia in Iranian families, identified by whole exome sequencing.

Sideroblastic anemias are heterogeneous rare hematological disorders, representing diverse phenotypes. In this study, the genetic cause of congenital, transfusion dependent anemia in four unrelated families consisting of eighteen individuals, with one affected member was investigated. Probands were suspected to rare anemias, including sideroblastic anemia. Whole exome sequencing in probands followed by segregation analysis in families was performed. Two novel frame shift mutations and one previously reported missense mutation in SLC25A38 gene was identified in these families. Mutations and their recessive mood of inheritance in each family were confirmed by PCR and Sanger sequencing. These findings suggest that sideroblastic anemia must be considered a possible etiology in cases with unexplained hemolytic anemia. Furthermore, mutations in SLC25A38 gene could be a prevalent cause of congenital sideroblastic anemia (CSA) in the Iranian population. Considering that parents of all affected individuals had consanguineous marriage and belong to sub populations, where consanguineous marriage is prevalent, it is important to perform carrier screening and genetic counseling in these families and their close relatives as prevention strategy in populations at risk.