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Maternal obesity
Published in Moshe Hod, Vincenzo Berghella, Mary E. D'Alton, Gian Carlo Di Renzo, Eduard Gratacós, Vassilios Fanos, New Technologies and Perinatal Medicine, 2019
Tahir A. Mahmood, Rohan Chodankar
In pregnancies with diabetes, proapoptotic and oxidative stress–related phenomena may explain the most prevalent malformations in offspring, which are hyperglycemia induced, even in the absence of maternal systemic disease. In pregnant rodent models with diabetes, the gene expression of protein kinase B (Akt), c-Jun-NH2-terminal kinase (JNK1/2), protein kinase R (PKR), and protein kinase C (PKC) is increased and is associated with neural tube defects. Excessive oxidative stress leads to activation of cell death cascade via apoptosis signal–regulating kinase 1 (ASK1), JNK1/2, transcription factor FoxO3a, tumor necrosis factor (TNF-1), and caspase-8 (80,81).
Mechanism of Action of Isotretinoin
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
FoxO1 also binds directly to the POMC promoter and negatively regulates its transcription. In addition, FoxO3a interacts with STAT3 and inhibits POMC promoter activity (52,53). Isotretinoin-induced upregulation of FoxO1 and FoxO3a may thus explain isotretinoin-mediated suppression of POMC-dependent pituitary gene expression, the precursor of ACTH. Isotretinoin-mediated upregulation of p53 attenuates androgen receptor (AR) gene expression (54). p53 and FoxO1 suppress AR expression and transactivation, respectively (55,56). This has been demonstrated in the skin of isotretinoin-treated acne patients, where isotretinoin has reduced AR expression as well as 5α-reductase activity in the skin, which has lost 80% of their ability to form 5α-dihydrotestosterone (57,58). In contrast, p53 deletion has activated AR signaling and restored c-MYC-induced differentiation in sebaceous glands (59). p53 is a negative regulator of thyroid hormone receptor-signaling pathways (60).
Micronutrients in Improvement of the Standard Therapy in Cancer
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Specific protein1 (SP1), a transcriptional factor, enhanced the expression of miR-182 that inhibited its target protein, PTEN, and promoted growth and reduced metastasis of cancer cells. In the late stage of cancer, the expression of SP1 and miR-182 decreased and the levels of FOXO3 enhanced, leading to lung metastasis.33 Lung cancer tissues and lung cancer cell lines have higher expression of miR-5100 and lower levels of its target protein Rab6 (Ras-related protein Rab6A) than normal tissues. Overexpression of this microRNA and reduced levels of its target protein Rab6 promoted growth of cancer in nude mice and enhanced the proliferation in cancer cell lines.34
Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis
Published in Pharmaceutical Biology, 2023
Xiaoyuan Xu, Xiaohua Xu, Xiaoshuang Wang, Ling Shen
Evidence has shown that FOXO proteins including FOXO1 and FOXO3 are involved in apoptosis and cell cycle regulation (Morris et al. 2015; Beretta et al. 2019). Thus, we investigated the effect of baicalin on the cell cycle distribution of KGN cells. As shown in Figure 6(A,B), baicalin considerably upregulated the level of p27 Kip1 in KGN cells, while this upregulation was partly reversed by miR-874-3p agomir or miR-144 agomir. As expected, baicalin-induced upregulation of p27 Kip1 in KGN cells was further suppressed by miR-874-3p agomir plus miR-144 agomir, compared to miR-874-3p agomir or miR-144 agomir alone treatment (Figure 6(A,B)). In addition, baicalin elevated the proportion of KGN cells in the G0-G1 phase and decreased the proportions of cells in the S phases; however, these phenomena were reversed by miR-874-3p agomir or miR-144 agomir (Figure 6(C,D)). Moreover, the expression of p27 Kip1 and cleaved caspase 3 was remarkably reduced in ovarian tissues of PCOS rats, compared to the control group (Figure 6(E–G)). However, baicalin treatment was able to reverse these effects (Figure 6(E–G)). Collectively, baicalin could suppress cell cycle progression in KGN cells via downregulating miR-874-3p and miR-144.
Foxo3a-Mediated DNMT3B Impedes Cervical Cancer Cell Proliferation and Migration Capacities through Suppressing PTEN Promoter Methylation
Published in Journal of Investigative Surgery, 2023
Hongying Li, Yuqin Yuan, Hong Dong, Tinghui Wang, Dunlan Zhang, Limin Zhou, Lu Chen, Xueyan He
To date, many articles reveal an anti-tumor function of FOXO3a on human diseases. For instance, upregulation of FOXO3a impairs tumor growth in breast cancer cells [20] and prostate cancer cells [21]. Meanwhile, inhibition of FOXO3a transcriptional activity in tumor cells contributes to the enhancement of tumor progression [22]. More importantly, FOXO3a has been considered to be a potent biomarker in cervical cancer [23–25]. Certain traditional factors such as FIGO stage, LMN, deep stromal infiltration as well as lymph-vascular space invasion are usually considered to be the prognostic factors of cervical cancer [26]. Here, the correlation between Foxo3a level and characteristics of cervical cancer suggested that Foxo3a level had a relationship with FIGO stage, differentiation degree, tumor diameter, as well as lymph node metastasis. Meanwhile, in our work, we observed that FOXO3a was expressed at a low level in cervical cancer, and its overexpression contributed to a reduction in cell proliferative, migratory, and invasive capabilities, and an elevation in apoptosis rate. Accordingly, upregulation of FOXO3a by demethylating agents can retard tumor growth in breast cancer cells [20]. Also, Foxo3a’s low expression reflects a poor prognosis of ovarian cancer patients, which could be an effective prognostic target in ovarian cancer [27]. All these findings confirmed the suppressive function of Foxo3a in gynecological diseases.
Pyroptosis in neurodegenerative diseases: What lies beneath the tip of the iceberg?
Published in International Reviews of Immunology, 2023
Mengli Yue, Li Xiao, Rui Yan, Xinyi Li, Wei Yang
As an crucial transcriptional regulator, Forkheadboxo (FoxO) family is related to a variety of cell functions. FoxO3a has been widely studied due to its unique and critical regulation in cell proliferation, apoptosis, metabolism, stress management and lifespan. Apoptosis repressor with caspase recruitment domain (ARC) is a cardinal downstream molecule of FoxO3a, which can inhibit the expression of inflammatory molecules [77]. A number of miRNAs are involved in the regulation of cell pyroptosis by targeting Foxo3a/ARC/caspase-1/IL-1 β and IL-18 axis. MiR-30d [57], miR-149 [58], miR-155 [59], miR-29b [60] attenuate the expression of FoxO3 by binding its 3’UTR. The dysfunction of FoxO3 destroys its subcellular distribution between nucleus and cytoplasm, thus the expression of downstream protein ARC is down-regulated, which relieves the inhibition of ARC on the expression of caspase-1 and pro-inflammatory cytokines IL-1 β and IL-18, therefore promote the pyroptosis.