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Biochemical Markers in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Abdus Samad Ansari, Pirro G. Hysi
DNA methylation (DNAm) is an attachment of a methyl group to the cytosine residue in the DNA. Somewhat reductively, we distinguish three separate molecular mechanisms involved in DNAm. The first, mediated primarily by DNMT3A and DNMT3B enzymes [79], methylates cytosine residues in previously unmethylated DNA. This process is of particular importance during early developmental stages and germline cell differentiation. This process causes cells to gradually lose their embryonic pluripotency and acquire methylation profiles that are characteristic of a specific line, organ, and tissue, distinct from other cell lines and tissues. Pluripotency and loss thereof, during cell differentiation processes, is controlled by not yet fully understood mechanisms and involves a small number of transcription factors. Among those, four transcription factors (Oct3/4, Sox2, Klf4, and Myc), the so-called Yamanaka factors [80], appear to act as master regulators. Tissue specificity arising since the earliest embryonic stages is a main feature of DNAm and is conserved across the different species [81].
Anatomy, physiology, and histology of the skin
Published in Michael Parker, Charlie James, Fundamentals for Cosmetic Practice, 2022
The process of differentiation of transit-amplifying cells is mediated by various signalling pathways to ensure that they differentiate into the correct cell types at the correct time and depth. Some of the better understood signalling pathways include Notch, C/EBP, MAPK, NF-κB, and KLF4. Failure for differentiation to occur properly can result in severe and potentially life-threatening diseases, such as Harlequin ichthyosis and dystrophic epidermolysis bullosa.
Central Nervous System
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Meningiomas present most commonly in middle age, more often in women (female:male = 3:2). They rarely occur in children, when they tend to be more aggressive. They can be induced by radiation and are associated with some genetic syndromes, particularly NF2. A majority of tumors show the presence of progesterone receptors, and a minority are estrogen receptor positive. Whether this is important in the etiology is not established. Loss of chromosome 22 and NF2 mutation or inactivation are common findings in sporadic meningioma. Next-generation sequencing has also demonstrated somatic mutations in TRAF7, KLF4, AKT1, SMO, and PIK3CA, which are mutually exclusive to NF2/Chr22 loss and align with histological subtypes and anatomical location. For example, meningothelial meningiomas are characterized by AKT1 mutations, and mutations in SMO and AKT1/TRAF7 are associated with anterior skull-base location.69
Lef1 is transcriptionally activated by Klf4 and suppresses hyperoxia-induced alveolar epithelial cell injury
Published in Experimental Lung Research, 2022
Min Yang, Xueshan Huang, Fang Shen, Juanjuan Yi, Yanni Meng, Yanping Chen
Klf4 functions as a transcription factor, regulating the transcription of target genes. To evaluate the link between Klf4 and Lef1, we utilized JASPAR (https://jaspar.genereg.net/) to predict probable Klf4 binding sites in the Lef1 promoter (Figure 3A). The luciferase test was used to validate the prediction. After co-transfecting oe-Klf4 and Lef1-WT or Lef1-MUT into MLE-12 cells, oe-Klf4 increased Lef1-WT luciferase activity but had no impact on Lef1-MUT (Figure 3B). Moreover, the ChIP assay revealed that Klf4 was enriched in the promoter of Lef1 (Figure 3C). These results revealed that Klf4 could bind to the promoter of Lef1, and hyperoxia increased the combination (Figure 3B and C). After transfection with oe-Klf4 in normoxia or hyperoxia treated MLE-12 cells, and the findings revealed that oe-Klf4 significantly increased Lef1 expression (Figure 3D) and LEF1 level (increased by 47% for normoxia condition and 1.1 times for hyperoxia condition; Figure 3E). It was concluded from these findings that Klf4 binds to Lef1’s promoter region and aids transcription.
Pluripotency inducing Yamanaka factors: role in stemness and chemoresistance of liver cancer
Published in Expert Review of Anticancer Therapy, 2021
Homa Fatma, Hifzur Rahman Siddique
Yamanaka factor KLF4 plays a vital role in maintaining chemoresistance in cancer cells both in vitro and in vivo. In KLF4 knockdown cells, chemotherapeutic treatment leads to a significant decrease in tumor size [99]. In HCC cells, KLF4 downregulates the expression of SLUG, an important regulator of EMT. EMT is associated with the induction of chemoresistance in various cancer cells, including liver cancer cells. It might strongly point toward the opposite effect of KLF4 in imparting chemoresistance [100]. Different molecules impart their influence on KLF4 through different pathways. It might be the reason for the debatable position of KLF4 in imparting cancer chemoresistance and providing chemosensitization. CSCs are associated with chemoresistance, and OSKM are key players in inducing stemness in tumor stem cell populations. A table tabulating the important stimulants targeting OSKM and their downstream targets is arranged in Table 2[6,14,81-82,93,94,95,101,102,103,104,105]. However, the range of involvement of OSKM in imparting therapy resistance to aggressive cancers is yet to be fully understood.
Silence of MEG3 intensifies lipopolysaccharide-stimulated damage of human lung cells through modulating miR-4262
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Xiaoliang Li, Qianqian Zhang, Zhigang Yang
MiRs are small non-coding RNAs that participate in physiology and disease through down-regulating target mRNAs [28]. The roles of miR-4262 in cell proliferation, migration and apoptosis are controversial due to the different target mRNAs [29,30]. Thus, we next screened the possible interacted genes of miR-4262 via bioinformatics methods. KLF4 is a conserved transcriptional factor that participates in multiple cellular processes, such as cell proliferation, migration and apoptosis [31]. KLF4 acts as either a tumor suppressor or an oncogene in diverse cancers, and the suppressive role of KLF4 in lung cancer has been proven [32]. In another literature, ALI could be ameliorated by miR-7 deficiency through up-regulating KLF4 [33]. Hence, in our study, we focused on the interaction between miR-4262 and KLF4. Results implied KLF4 was negatively correlated with miR-4262 level and KLF4 overexpression could alleviate LPS-induced WI-38 cell injury. The protective role of KLF4 overexpression in LPS-treated WI-38 cells was consistent with the literature described above [33]. On the basis of the above results, it can be suggested that MEG3 knockdown might aggravate LPS-induced WI-38 cell injury through miR-4262-mediated down-regulation of KLF4.