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Islet Transplantation in Type 1 Diabetes: Stem Cell Research and Therapy
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
During the embryogenesis in mice, the epiblast is derived from the inner cell mass of the blastocysts during gastrulation, which gives rise to principal germ layers-ectoderm, endoderm and mesoderm. Mesendodermal cells regulate the expression of several genes such as Brachyury (T) and Mixl1 which control differentiation of definitive endoderm and mesoderm progenitors. Pancreas arises from definitive endoderm (DE) as a flat sheet of cells that is specified during gastrulation [30, 31].
Screening of prognostic risk microRNAs for acute myeloid leukemia
Published in Hematology, 2018
Hai-Yan Gao, Wei Wang, Xin-Guo Luo, Yong-Fang Jiang, Xin He, Ping Xu, Xi Chen, Xiao-Yun Li
Hsa-mir-520a was predicted to be the most important risk factor for AML prognosis. Previously, its down-regulation has been reported to correlate with the Imatinib resistance in chronic myeloid leukemia patients [21], but its role in AML has never been reported so far. In the present study, this miRNA was speculated to increase the prognostic risk of AML via regulating various genes, especially EGFR, REL, COL14A1 and HDAC3. Among them, EGFR (epidermal growth factor receptor) was enriched into four pathways, namely endocytosis, regulation of actin cytoskeleton, erbB signalling pathway and pathways in cancer. In the latter two pathways, Akt is a downstream gene. Scheepers et al. have reported that inhibition of EGFR activity can reduce the AML cell survival via inhibition of downstream Akt and Erk proteins [22]. In addition, small molecule EGFR-targeted therapy in AML patients such as erlotinib may be related to the inhibition of oncogenic signalling via SRC family kinases and mTOR (downstream signal of Akt) [23]. Given that the outcome of inhibition of EGFR is similar to a down-regulation of its expression level, it may be inferred that higher EGFR expression level might be conducive to the survival of AML cells, further suggesting that hsa-mir-520a might increase the prognostic risk of AML via up-regulating the EGFR level. The proto-oncogene REL encodes c-REL, a transcription factor that is a member of the Rel/NFKB family [24]. c-REL has been reported to be a transcriptional target of MIXL1 (Mesoderm Inducer in Xenopus Like 1), a critical regulator of embryonic and adult hematopoiesis, by Raymond et al. who proposed that the up-regulation of REL by MIXL1 promoted the survival or proliferation of AML cells via activating the Nf-κB pathway [25]. This suggests that hsa-mir-520a might also increase the prognostic risk of AML via up-regulating REL expression. COL14A1 encodes the alpha chain of type XIV collagen that is involved in cell adhesion. It was observed to be up-regulated in DAC (decitabine)-treated AML cells and DAC can induce AML remission via reducing the genomic DNA methylation [26]. This was consistent with the speculation that hsa-mir-520a might increase the AML prognostic risk via down-regulating COL14A1. HDAC3 (histone deacetylase 3) is one of the four members of the human class I HDACs that catalyze the removal of acetyl groups from lysine residues in histones and nonhistone proteins [27]. Wada et al. have experimentally observed HDAC overexpression and histone hypoacetylation in AML cell lines [28]. Lepore et al. have reported HDAC inhibitor Vorinostat reduces the expression level of BARD1 (BRCA1-associated RING domain 1) isoforms that might act as oncogenes via elevating the expression of miR-19a and miR-19b in AML cells [29]. Thus, it is presumably that high HDAC level may be responsible for the overexpression of BARD1 isoforms. It can be further inferred that miR520a may increase the prognostic risk of AML by increasing HDAC expression level.