Colorectal cancer (CRC) is one of the most common malignant diseases worldwide, but the involved signaling pathways and driven-genes are largely unclear. This study integrated four cohorts profile datasets to elucidate the potential key candidate genes and pathways in CRC. Expression profiles GSE28000, GSE21815, GSE44076 and GSE75970, including 319 CRC and 103 normal mucosa, were integrated and deeply analyzed. Differentially expressed genes (DEGs) were sorted and candidate genes and pathways enrichment were analyzed. DEGs-associated protein–protein interaction network (PPI) was performed. Firstly, 292 shared DEGs (165 up-regulated and 127 down-regulated) were identified from the four GSE datasets. Secondly, the DEGs were clustered based on functions and signaling pathways with significant enrichment analysis. Thirdly, 180 nodes/DEGs were identified from DEGs PPI network complex. Lastly, the most significant 2 modules were filtered from PPI, 31 central node genes were identified and most of the corresponding genes are involved in cell cycle process, chemokines and G protein-coupled receptor signaling pathways. Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in CRC, which could improve our understanding of the cause and underlying molecular events, and these candidate genes and pathways could be therapeutic targets for CRC.
Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic β cell failure. β cell factors are traditionally thought to control glucose homeostasis by modulating insulin levels, not insulin sensitivity. Exosomes are emerging as new regulators of intercellular communication. However, the role of β-cell-derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in β cells not only modulates insulin secretion and β cell replication in an autocrine manner but also regulates peripheral insulin sensitivity in a paracrine manner through circulating exosomes. MiR-26a is reduced in serum exosomes of overweight humans and is inversely correlated with clinical features of T2D. Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice. Using miR-26a knockin and knockout mouse models, we showed that miR-26a in β cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in β cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and β cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of β cells and offer opportunities for the treatment of T2D.
Cadmium (Cd) accumulation in rice grain poses a serious threat to human health. While several transport systems have been reported, the complexity of rice Cd transport and accumulation indicates the necessity of identifying additional genes, especially those that are responsible for Cd accumulation divergence between
indica
and
japonica
rice subspecies. Here, we show that a gene,
OsCd1
, belonging to the major facilitator superfamily is involved in root Cd uptake and contributes to grain accumulation in rice. Natural variation in
OsCd1
with a missense mutation Val449Asp is responsible for the divergence of rice grain Cd accumulation between
indica
and
japonica
. Near-isogenic line tests confirm that the
indica
variety carrying the
japonica
allele
OsCd1
V449
can reduce the grain Cd accumulation. Thus, the
japonica
allele
OsCd1
V449
may be useful for reducing grain Cd accumulation of
indica
rice cultivars through breeding.
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