Regulation of erythroid differentiation by miR-376a and its targets

Wang, Fang; Yu, Jia; Yang, Guihua; Wang, Xiaoshuang; Zhang, Jun-Wu

doi:10.1038/cr.2011.79

Cited by 53 publications

(45 citation statements)

References 44 publications

(60 reference statements)

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“…Western blot was performed as described with modifications [37]. Briefly, total cellular proteins were extracted from NP cells with the lysis buffer and separated on 10% SDS-PAGE gel.…”

Section: Methodsmentioning

confidence: 99%

Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

Shen

et al. 2012

PLoS ONE

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Increasing evidence suggests that obesity and aberrant proliferation of nucleus pulposus (NP) cells are associated with intervertebral disc degeneration. Leptin, a hormone with increased circulating level in obesity, has been shown to stimulate cell proliferation in a tissue-dependent manner. Nevertheless, the effect of leptin on the proliferation of human NP cells has not yet been demonstrated. Here, we show that leptin induced the proliferation of primary cultured human NP cells, which expressed the leptin receptors OBRa and OBRb. Induction of NP cell proliferation was confirmed by CCK8 assay and immunocytochemistry and Real-time PCR for PCNA and Ki-67. Mechanistically, leptin induced the phosphorylation of STAT3, Akt and ERK1/2 accompanied by the upregulation of cyclin D1. Pharmacological inhibition of JAK/STAT3, PI3K/Akt or MEK/ERK signaling by AG490, Wortmannin or U0126, respectively, reduced leptin-induced cyclin D1 expression and NP cell proliferation. These experiments also revealed an intricate crosstalk among these signaling pathways in mediating the action of leptin. Taken together, we show that leptin induces human NP cell cyclin D1 expression and proliferation via activation of JAK/STAT3, PI3K/Akt or MEK/ERK signaling. Our findings may provide a novel molecular mechanism that explains the association between obesity and intervertebral disc degeneration.

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“…Western blot was performed as described with modifications [37]. Briefly, total cellular proteins were extracted from NP cells with the lysis buffer and separated on 10% SDS-PAGE gel.…”

Section: Methodsmentioning

confidence: 99%

Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

Shen

et al. 2012

PLoS ONE

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“…For instance, miR-376a, with adjacent miRNA in the same cluster, was identified as a potential tumor suppressor in human epithelial ovarian cancer [28]. miR-376a was also reported to repress erythroid cell cycle progression and cell growth by targeting cyclin dependent kinase 2 (CDK2) and Ago2 [29], resulting in erythroid differentiation inhibition. Coincidence with previous studies, our study suggests that miR-376a suppresses cell proliferation in HCC.…”

Section: Discussionmentioning

confidence: 99%

miR‐376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

Zheng

Chen

et al. 2012

FEBS Letters

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MicroRNAs are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aims to explore the potential biological function of miR-376a, which was found to be inhibited after partial hepatectomy, in HCC. We discovered that miR-376a was frequently down-regulated in HCC cell lines and HCC tissues, while higher relative level of miR-376a was significantly associated with high serum AFP level. Over-expression of miR-376a not only inhibited proliferation but induced apoptosis in Huh7 cells. Additionally, p85α (PIK3R1) was identified as a direct and functional target of miR-376a in Huh7 cells. Moreover, we confirmed that p85α and miR-376a were inversely correlated in HCC. These findings suggest that down-regulation of miR-376a may contribute to the development of HCC by targeting p85α.

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“…This interaction reduces the expression levels of GATA1 protein and, consequently, represses hematopoiesis when miR‐152 is overexpressed . In mammals, regulation of GATA‐1 levels by microRNAs has not been validated yet, including miRNAs that have been described to modulate erythropoiesis …”

Section: Regulation Of Gata1 Mrna Translationmentioning

confidence: 99%

Regulation of GATA1 levels in erythropoiesis

et al. 2019

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GATA1 is considered as the "master" transcription factor in erythropoiesis. It regulates at the transcriptional level all aspects of erythroid maturation and function, as revealed by gene knockout studies in mice and by genome-wide occupancies in erythroid cells. The GATA1 protein contains two zinc finger domains and an N-terminal transactivation domain. GATA1 translation results in the production of the full-length protein and of a shorter variant (GATA1s) lacking the N-terminal transactivation domain, which is functionally deficient in supporting erythropoiesis. GATA1 protein abundance is highly regulated in erythroid cells at different levels, including transcription, mRNA translation, posttranslational modifications, and protein degradation, in a differentiationstage-specific manner. Maintaining high GATA1 protein levels is essential in the early stages of erythroid maturation, whereas downregulating GATA1 protein levels is a necessary step in terminal erythroid differentiation. The importance of maintaining proper GATA1 protein homeostasis in erythropoiesis is demonstrated by the fact that both GATA1 loss and its overexpression result in lethal anemia. Importantly, alterations in any of those GATA1 regulatory checkpoints have been recognized as an important cause of hematological disorders such as dyserythropoiesis (with or without thrombocytopenia), β-thalassemia, Diamond-Blackfan anemia, myelodysplasia, or leukemia. In this review, we provide an overview of the multilevel regulation of GATA1 protein homeostasis in erythropoiesis and of its deregulation in hematological disease. K E Y W O R D S

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Regulation of erythroid differentiation by miR-376a and its targets

Cited by 53 publications

References 44 publications

Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

miR‐376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

Regulation of GATA1 levels in erythropoiesis

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