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Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
Genes activated by RA are members of different signaling pathways including TGF-β pathway (genes left-right determination factor 2 [LEFTY2], BMP and activin membrane bound inhibitor [BAMBI], Follistatin [FST]), homeodomain pathway (genes HoxD1, MEIS1, MEIS2), gastrulation brain homeobox 2 (GBX2), insulin growth factor (IGF) pathway (genes IGFBP3, IGFBP6, CTGF), Notch pathway (genes manic fringe [MFNG] and metallopeptidase domain 11 [ADAM11]), Hedgehog pathway (gene Patched [PTCH]) and Wnt pathway (genes FRAT2 and secreted frizzled-related protein 1 [SFRP1]) (19). In addition, transcription factors from Sry-related HMG box (SOX) gene family are upregulated during the RA induced neural differentiation, such as SOX3, one of the earliest neural markers (28). It has been postulated that cumulative regulation of SOX target genes during neurogenesis is the result of a fine balance between gene expression control regulated by members of SOXB1 (SOX1, SOX2, SOX3) and SOXB2 (SOX14 and SOX21) gene subfamilies (29–31). The increase in SOXB2 protein levels activates proneural proteins, which subsequently interfere with SOXB1 function, leading to differentiation of a neural progenitor towards neuronal phenotype (29). Members of SOXB subfamily are directly (32–34) and indirectly (35–37) regulated by RA and RA effector signaling. SOXB protein expression changes during the course of differentiation (20), which makes them a group of genes that participate in RA mediated proliferation-differentiation switches.
Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma
Published in Chronobiology International, 2023
Lei Qian, Xiaochen Ding, Xiaoyan Fan, Shisen Li, Yihuan Qiao, Xiaoqun Zhang, Jipeng Li
It is believed that SOX14, a member of the SRY-related HMG box class of transcription factors, functions as a transcriptional repressor to control neuron lineage fate (Hargrave et al. 2000). Indeed, DLX2−, HELT+, TAL1+, and SOX14+ neurons located in the diencephalon are progenitors of GABAergic cells in the subcortical visual shell (SVS), mediating the formation of the SVS network by promoting tangential migration of GABAergic progenitors. Furthermore, impaired SOX14 function leads to anatomical defects in the SVS, which is an important regulator of the circadian rhythmic behavior; therefore, SOX14 expression can, to a certain extent, ensure the stability of circadian rhythms (Delogu et al. 2012). Recent studies have found that SOX14 is also involved in tumor progression. De S et al. found that SOX14 can inhibit apoptosis in cervical cancer cell lines by activating the p53 pathway (Stanisavljevic et al. 2017). Li et al. (2015) showed that SOX14 contributes to the proliferation and invasion of cervical cancer cells through the Wnt/β-catenin pathway.
Identification of potential ‘lifestyle-responsive’ epigenomic biomarkers in healthy women aged 18–40
Published in Biomarkers, 2018
Michelle Thunders, Victoria Chinn, Jaret Bilewitch, Peter Stockwell
When analysed at an individual level as illustrated in Table 4, 10 of the 21 women who participated in the invention had a greater proportion of differentially methylated genes with lower methylation at the six-month time point. Two had the same proportion of differentially methylated genes and nine had a higher proportion of differentially methylated genes that had higher methylation post intervention. This was not the same in the small control group. It is difficult to make conclusions from this data but it is possible the intervention had caused an overall decrease in methylation in line with genes becoming more active as a consequence of the lifestyle changes. There are many genes identified in common in all the women that were higher in some and lower in others hence not identified through the ANOVA analysis of the whole group, for example, if we look at Sex Determining Region Y-Box 14 (SOX14) on chromosome 3, this is highlighted as differentially methylated in all the women, including the group of three non-participants but varied from women to women as to whether this was differentially higher or lower methylated over the six-month period. SOX14 is a transcription factor and has been found to be greatly upregulated in cervical cell growth in cancer (Li et al.2015), with a putative role as an oncogene. The variation in methylation we see in this study could relate to normal ovarian cell growth/inhibition relative to stage in the female menstrual cycle. There are some genes, such as Transmembrane Phosphatase With Tensin Homology (TPTE) on chromosome 21 identified as both higher and lower post intervention in the same individual, relating to more than one CpG site associated with a particular gene in the vicinity of the CpG site highlighted, these could represent important areas in complex gene regulation pathways or methylation hotspots.