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enn diagram of miRNA interactions depending on the overlapping miRNAs among the 4 groups.11p15.5 and correlates with angiogenesis and VEGF regulation in breast cancer individuals (Forkens et al., 2008; Dai et al., 2015; Tang et al., 2018; Zhang H. et al., 2019). Inside the present study, the expression of miR-210-x and miR-210-z was drastically reduced in TH than in TL but not substantially distinctive inside the other groups, which might play AChE Antagonist medchemexpress crucial roles in the expression of proteins in homology-dependent repair pathways and nucleotide excision repair pathways to reverse cellular DNA damage in the lungs of Tibetan pigs in the course of hypoxia (Crosby et al., 2009; Hui et al., 2019). HBB is involved within the malaria reference pathway and downregulates IL-6, which can be a key gene in the HIF-1 pathway. Comparison of HBB expression among Tibetan pigs and Landrace pigs showed that amongst the beta globin amino acid substitutions at positions 58, 75, 119 and 137, the replacement of alanine at position 137 with valine as well as the locus mutation improved the affinity of HGB and O2 (Zhang B. et al., 2016). The expression in the HBB gene in Tibetan pigs (TH and TL) was drastically higher than that in Landrace pigs (LH and LL), agreeing having a comparable trend previously reported by other authors, and there was similar variation inthe HGB concentration in Tibetan pigs (Taliercio et al., 2013; Zhang B. et al., 2016; Yang et al., 2021), indicating that hypoxia transcriptionally upregulates HBB to raise HGB inside the blood to ensure the transport of blood and nutrients. These findings may perhaps (Jang et al., 2014; Zhang G. et al., 2016; Cai et al., 2018) explain why Tibetan pigs have superior adaption than Landrace pigs in hypoxic environments no matter altitude. The PI3K/Akt pathway is definitely an intracellular signaling pathway which is promoted by many biological molecules, which includes calmodulin, insulin-like development issue (IGF), and multiple EGFlike domains six (MEGF6) (Pompura and Dominguez-Villar, 2018; Ellis and Ma, 2019; Revathidevi and Munirajan, 2019; Zhang et al., 2020). IGF2 may be the target gene of miR-506y and ssc-miR-181d-3p. The expression levels of IGF2 and MEGF6 had been substantially upregulated in LH compared to LL, but no variations have been discovered inside the Tibetan pigs (TH and TL). We hypothesized that these genes may perhaps induce the growth, proliferation, and differentiation of tumor cells within the lungs of Landrace pigs living within a hypoxic environment (Mohlin et al., 2013). Activated Akt induces several biologicalFrontiers in Genetics | frontiersin.orgOctober 2021 | Volume 12 | ArticleYang et al.Response of Tibetan Pigs’ Lung to HypoxiaFIGURE 7 | Integrated miRNA-target damaging correlation regulatory network. The square nodes represent miRNAs, and the circle nodes represent target genes. The differentially expressed miRNAs/target genes are highlighted as follows: red indicated SIRT2 manufacturer differential expression among Landrace pigs raised in lowlands (LL) and Landrace pigs raised in highland (LH), green indicates differential expression among LH and Tibetan pigs raised in highland (TH), blue indicates differential expression between TH and Tibetan pigs raised in lowland (TL), and purple indicates differential expression amongst TL and LL.processes, including activating mTOR, localizing FOXO for the cytoplasm, and activating cAMP-response element binding protein (CREB) (Zhang et al., 2011; Gaec -Morales et al., 2017;Marquard and J ker, 2020). The FOXO signaling pathway was also enriched within a compariso

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