Transcription factor STOX1 regulates proliferation of inner ear epithelial cells <i>via</i> the AKT pathway

Nie, Xiaowei; Zhang, Kaiqing; Wang, Li; Ou, Guangshuo; Zhu, He; Gao, Wei‐Qiang

doi:10.1111/cpr.12174

Cited by 22 publications

(17 citation statements)

References 45 publications

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“…Thus, we focused on Stox1. Stox1 is a transcription factor belonging to the enlarged Forkhead Box gene family that has been associated with preeclampsia (van Dijk et al, ), central nervous system (Abel, Abdul‐Hamid, Dijk, & Oudejans, ; Feng et al, ) and inner ear epithelial cells development (Nie et al, ), palys a significant role in cell proliferation and migration (Nie et al, ; van Dijk et al, ). Second, it is reported that there are endothelial cell dysfunction and cardiac hypertrophy in the Stox1 model of preeclampsia (Ducat et al, ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA‐TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism

Liu

Sun

Zhu

et al. 2018

Journal Cellular Physiology

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Long noncoding RNAs (lncRNAs) have been discovered to be playing important role in various biological processes. However, the contribution of lncRNAs to pulmonary artery hypertension (PAH) remains largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Here, we investigated the biological role of lncRNAs in PAH. Differences in the lncRNAs and mRNAs between hypoxia PAH rats and normoxia rats were screened using microarray analysis. The results showed that 36 lncRNAs and 519 mRNAs were upregulated in the pulmonary arteries (PAs) of hypoxia PAH rats, whereas 111 lncRNAs and 246 mRNAs were downregulated. Expressions of the screened lncRNAs, including TCONS_00034812, were validated by real-time PCR. We revealed that the expression of TCONS_00034812 was significantly downregulated in PAs of PAH rats and hypoxia pulmonary artery smooth muscle cells (PASMCs). TCONS_00034812 knockdown promoted proliferation and inhibited apoptosis of PASMCs in vitro. Moreover, TCONS_00034812 regulated PASMCs function in vitro. We found that TCONS_00034812 increased the expression of transcription factors Stox1. TCONS_00034812 and Stox1 knockdown mediated PASMCs function through MAPK signaling. Our findings imply lncRNA as a critical regulator in PAH and demonstrate the potential of gene therapy and drug development for treating PAH. The present study reveals a novel mechano responsive lncRNA-TCONS_00034812, which modulates PASMCs proliferation and apoptosis, and participates in vascular remodeling during PAH.

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Section: Discussionmentioning

confidence: 99%

LncRNA‐TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism

Liu

Sun

Zhu

et al. 2018

Journal Cellular Physiology

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“…Gata2 is critical for vestibular organ morphogenesis ( Haugas et al, 2010 ). Stox1 is selectively expressed in the cochlear sensory epithelium, and overexpression of Stox1 enhances cell proliferation and sphere formation ( Nie et al, 2015 ), suggesting that Stox1 might be one of the genes leading to the greater proliferation ability of Lgr5+ progenitors. Genes highly expressed in Lgr6+ progenitors compared to Lgr5+ progenitors include Adk and Otoa .…”

Section: Discussionmentioning

confidence: 99%

Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea

Zhang

Guo

Lü

et al. 2018

Front. Mol. Neurosci.

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Hair cell (HC) loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/β-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5, Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs. Our previous studies showed that Lgr6+ cells are a subpopulation of Lgr5+ progenitor cells and that both Lgr6+ and Lgr5+ progenitors can generate Myosin7a+ HCs in vitro. Thus we hypothesized that Lgr6+ cells are an enriched population of cochlear progenitor cells. However, the detailed distinctions between the Lgr5+ and Lgr6+ progenitors are unclear. Here, we systematically compared the proliferation, HC differentiation, and detailed transcriptome expression profiles of these two progenitor populations. We found that the same number of isolated Lgr6+ progenitors generated significantly more Myosin7a+ HCs compared to Lgr5+ progenitors; however, Lgr5+ progenitors formed more epithelial colonies and more spheres than Lgr6+ progenitors in vitro. Using RNA-Seq, we compared the transcriptome differences between Lgr5+ and Lgr6+ progenitors and identified a list of significantly differential expressed genes that might regulate the proliferation and differentiation of these HC progenitors, including 4 cell cycle genes, 9 cell signaling pathway genes, and 54 transcription factors. In conclusion, we demonstrate that Lgr6+ progenitors are an enriched population of inner ear progenitors that generate more HCs compared to Lgr5+ progenitors in the newborn mouse cochlea, and the our research provides a series of genes that might regulate the proliferation of progenitors and HC generation.

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“…Doridot L et al have found that STOX1 can play a genetic switch in the nitroso-redox balance and mitochondrial homeostasis (Doridot et al, 2014). Furthermore, STOX1 was also found to involve inner ear epithelial cell proliferation as a novel stimulatory factor activated by phosphorylation of protein kinase B pathway (Nie et al, 2015). LDH is a degenerative disease related F I G U R E 1 Haplotype block map for part of the SNPs in the STOX1.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the STOX1 polymorphism on lumbar disc herniation

Yang

Xin

et al. 2019

Molec Gen & Gen Med

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Background: Lumbar disc herniation (LDH) is a common musculoskeletal disorder affliction and associated with several genes polymorphism. Storkhead box 1 (STOX1) gene is a transcriptional factor related with several signaling pathways including inflammatory pathway. However, little is known about single-nucleotide polymorphisms (SNPs) of STOX1 associated with LDH risk. Methods: We conducted a case-control study among 508 LDH cases and wellmatched 508 controls, and six candidate SNPs in STOX1 were genotyped by Agena MassARRAY. Chi-squared test, genetic model, and haploview analysis were used to evaluate associations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. Results: In the allelic model analysis, we found the minor allele "T" of rs7903209 and "A" of rs4472827 were associated with an increased risk of LDH (p = .029, p = .016). Furthermore, in the genotype model analysis, rs7903209 polymorphism was associated with the increased susceptibility of LDH based on dominant (p = .033) and additive model (p = .024); and rs4472827 variant was found to play a harmful role in the LDH risk based on genotype (p = .014), dominant (p = .012), and additive model (p = .015). In the haplotype analysis, the haplotype "GT" in block (rs10998461 and rs10998468) decreased LDH risk (OR = 0.7, 95% CI = 0.52-0.93, p = .016). Functional assessment indicated that rs7903209 and rs4472827 polymorphisms may influence the expression of STOX1. Conclusion: Our results provide evidence for polymorphisms of rs7903209 and rs4472827 in STOX1 associated with LDH risk in Chinese Han population. K E Y W O R D Sgene expression, lumbar disc herniation, polymorphism, STOX1

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Transcription factor STOX1 regulates proliferation of inner ear epithelial cells via the AKT pathway

Abstract: Taken together, we demonstrate that STOX1 is a novel stimulatory factor for inner ear epithelial cell proliferation and might be an important target to be considered in regeneration or repair of inner ear epithelium.

Cited by 22 publications

References 45 publications

LncRNA‐TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism

LncRNA‐TCONS_00034812 in cell proliferation and apoptosis of pulmonary artery smooth muscle cells and its mechanism

Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea

Investigation of the STOX1 polymorphism on lumbar disc herniation

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