Leukemia inhibitory factor regulates marmoset induced pluripotent stem cell proliferation via a PI3K/‌Akt‑dependent Tbx‑3 activation pathway

Ke, Minxia; He, Quan; Hong, Danping; Ouyang, Liang; Zhu, Mengyiï¿1⁄2; Ou, Wen‐Bin; He, Yulong; Wu, Yuehong

doi:10.3892/ijmm.2018.3610

Cited by 9 publications

(8 citation statements)

References 42 publications

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“…6). These data was in line with previous ndings that miR-29 was expressed during active pulmonary tuberculosis [23], while miR-23, miR-29, miR-145, and miR -452 were either up-or downregulated in chronic obstructive pulmonary disease (COPD), non-small cell lung cancer (NSCLC) and in ammatory responses [24][25][26][27].…”

Section: Conserved Mirnassupporting

confidence: 91%

Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

jing

Jiang

Cheng

et al. 2021

Preprint

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Background: Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection remains a major public health burden worldwide. It has been well documented that a group of small noncoding RNAs, microRNAs (miRNAs) are involved in the development and pathogenesis many diseases, including the TB. Guinea pigs are considered as one of the best animal models for biomedical research in TB, the potential roles of miRNAs in the innate immune regulation of guinea pig lung against Mtb infection are not well understood. Methods: In this study, we investigated the differential expression of miRNA profiles between the un-infected lungs and Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected lungs of guinea pigs via deep sequencing and bioinformatics analysis. Results: A total of 2508 miRNAs were identified, among them 1187 were conserved miRNAs and 56 were novel miRNAs in the uninfected lungs, and 1202 were identified as conserved miRNAs and 63 were novel miRNAs in the BCG-infected lungs. Interestingly, comparison analysis further identified 902 co-expressed miRNAs and 585 distinct miRNAs between these two groups. Of the 15 most abundantly conserved miRNAs in guinea pig lungs, which belong to 7 miRNA families, including miR23, miR29, miR145, miR320, miR378, miR451, and miR423. 13 of these 15 most abundant miRNAs were significantly downregulated and 2 of them were significantly upregulated in the BCG-infected lungs. Individually, miRNA Let-7f-5p, let-7f, let-7-5p and let-7b-5p were the most abundant in both profiles of the non-infected and BCG-infected guinea pig lungs. The predicted target genes of specific miRNAs found in guinea pig lungs were involved in regulation signaling pathways related to immune responses, including Toll-like receptors (TLRs), nuclear factor (NF)-kappa B, Wnt, mitogen-activated protein kinase (MAPK), and transforming growth factor (TGF)-beta signaling, as well as related to autophagy signaling mTOR and apoptotic molecule p53. Conclusions: These data of comprehensive analysis of miRNA transcriptome demonstrated the differential expression profiles of miRNAs during M. tuberculosis infection of guinea pig lungs. These results could facilitate the future exploitation of the roles of miRNAs in regulation of immune responses to M. tuberculosis infection using the guinea pig model.

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Section: Conserved Mirnassupporting

confidence: 91%

Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

jing

Jiang

Cheng

et al. 2021

Preprint

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“…AKT activation enhances the reprogramming of somatic cells into iPSCs [20–22], and our study showed that overexpression of PBX1 activated the AKT/GSK3β signaling pathway, suggesting a role for PBX1 in reprogramming of HF-MSCs into HF-iPSCs. Indeed, the qPCR analysis showed that endogenous PBX1 levels increased with time during HF-iPSC reprogramming induced by SOMK transduction (Fig.…”

Section: Resultsmentioning

confidence: 71%

“…AKT activation can upregulate glucose transporters and metabolic enzymes involved in glycolysis, thereby enhancing the generation of iPSCs from human somatic cells [19, 20]. In the primate iPSC pluripotency network, the AKT pathway significantly upregulates T-box 3, a known transcriptional repressor that interacts with the pluripotency factors NANOG and OCT4 to promote the maintenance of pluripotency [21, 22]. Moreover, the AKT/GSK3β pathway is involved in β-catenin phosphorylation and regulates β-catenin to affect ubiquitin-mediated protein degradation.…”

Section: Introductionmentioning

confidence: 99%

PBX homeobox 1 enhances hair follicle mesenchymal stem cell proliferation and reprogramming through activation of the AKT/glycogen synthase kinase signaling pathway and suppression of apoptosis

et al. 2019

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Background PBX homeobox 1 (PBX1) is involved in the maintenance of the pluripotency of human embryonic and hematopoietic stem cells; however, the effects of PBX1 in the self-renewal and reprogramming of hair follicle mesenchymal stem cells (HF-MSCs) are unclear. The AKT/glycogen synthase kinase (GSK) 3β pathway regulates cell metabolism, proliferation, apoptosis, and reprogramming, and p16 and p21, which act downstream of this pathway, regulate cell proliferation, cell cycle, and apoptosis induced by reprogramming. Here, we aimed to elucidate the roles of PBX1 in regulating the proliferation and reprogramming of HF-MSCs. Methods A lentiviral vector designed to carry the PBX1 sequence or PBX1 short hairpin RNA sequence was used to overexpress or knock down PBX1. The roles of PBX1 in proliferation and apoptosis were investigated by flow cytometry. Real-time polymerase chain reaction was performed to evaluate pluripotent gene expression. Dual-luciferase reporter assays were performed to examine the transcriptional activity of the NANOG promoter. Western blotting was performed to identify the molecules downstream of PBX1 involved in proliferation and reprogramming. Caspase3 activity was detected to assess HF-MSC reprogramming. The phosphatidylinositol 3-kinase/AKT inhibitor LY294002 was used to inhibit the phosphorylation and activity of AKT. Results Overexpression of PBX1 in HF-MSCs increased the phosphorylation of AKT and nuclear translocation of β-catenin, resulting in the progression of the cell cycle from G 0 /G 1 to S phase. Moreover, transfection with a combination of five transcription factors (SOMKP) in HF-MSCs enhanced the formation of alkaline phosphatase-stained colonies compared with that in HF-MSCs transfected with a combination of four transcription factors (SOMK). PBX1 upregulated Nanog transcription by activating the promoter and promoted the expression of endogenous SOX2 and OCT4 . Furthermore, PBX1 expression activated the AKT/glycogen synthase kinase (GSK) 3β pathway and reduced apoptosis during the early stages of reprogramming. Inhibition of phospho-AKT or knockdown of PBX1 promoted mitochondrion-mediated apoptosis and reduced reprogramming efficiency. Conclusions PBX1 enhanced HF-MSC proliferation, and HF-MSCs induced pluripotent stem cells (iPSC) generation by activating the AKT/GSK3β signaling pathway. During the reprogramming of HF-MSCs into HF-iPSCs, PBX1 activated the NANOG promoter, upregulated NANOG , and inhibited mitochondrion-mediated apoptosis via the AKT/GSK3β pathway during the early stages of reprogramming.

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“… 21 Previously, TBX3 as another member of TBX family was found to be associated with the PI3K/AKT pathway. 22 Moreover, it is demonstrated that TBX1 functions as a tumor suppressor in thyroid cancer by inhibiting activation of the PI3K/AKT pathway. 23 Therefore, we speculated that TBX5-AS1 might participate in NSCLC progression through the PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

<p>LncRNA <em>TBX5-AS1</em> Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer</p>

Qing-hai¹,

Jiang²,

Li³

2020

OTT

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Long non-coding RNAs (lncRNAs) have been reported to play important roles in tumor biology. In this study, we aimed to investigate the effects of T-box transcription factor 5 antisense RNA 1 (TBX5-AS1) on aggressive phenotypes of non-small cell lung cancer (NSCLC) cells and explore its regulatory pathway. Methods: The expression of TBX5-AS1 in tissues, plasma, and cells was determined by qRT-PCR. Cell viability, proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, wound-healing, Transwell, and flow cytometry assay, respectively. Western blot analysis was performed to measure the expression of apoptosis-related proteins. Besides, transfected cells were exposed to PI3K activator (740Y-P) to verify the regulatory pathway. Results: TBX5-AS1 expression was down-regulated in NSCLC tissues, plasma, and cells, and associated with lymph node metastasis and histological grade. Overexpression of TBX5-AS1 inhibited cell viability, colony formation, migration, and invasion, while it promoted apoptosis. Conversely, knockdown of TBX5-AS1 showed the completely opposite results. Additionally, western blot showed that the phosphorylation of PI3K and AKT was stimulated by TBX5-AS1 knockdown and suppressed by TBX5-AS1 overexpression. The addition of 740Y-P in transfected cells reversed the TBX5-AS1induced inhibition of PI3K and AKT phosphorylation and effects on aggressive phenotypes of NSCLC cells. Conclusion: The study confirmed the down-regulation of TBX5-AS1 in patients with NSCLC and its association with the progression. We innovatively proposed a possible model of TBX5-AS1-mediated gene regulation in NSCLC progression that TBX5-AS1 inhibited the aggressive phenotypes of NSCLC cells through inactivating the PI3K/AKT pathway. This finding provided a novel insight into NSCLC pathogenesis.

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Leukemia inhibitory factor regulates marmoset induced pluripotent stem cell proliferation via a PI3K/‌Akt‑dependent Tbx‑3 activation pathway

Cited by 9 publications

References 42 publications

Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

Deep Sequencing of Guinea Pig (Cavia Porcellus) Lung Small RNAs Reveals Differential Expression of microRNAs between Non-infected and BCG-Infected Lungs

PBX homeobox 1 enhances hair follicle mesenchymal stem cell proliferation and reprogramming through activation of the AKT/glycogen synthase kinase signaling pathway and suppression of apoptosis

<p>LncRNA <em>TBX5-AS1</em> Regulates the Tumor Progression Through the PI3K/AKT Pathway in Non-Small Cell Lung Cancer</p>

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