Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells

Wang, Yu; Jin, Wei; Jia, Xiaohong; Luo, Renshi; Tan, Yun; Zhu, Xuehua; Yang, Xian‐Wen; X, Wang; Wang, K

doi:10.1038/cddis.2014.388

Cited by 35 publications

(30 citation statements)

References 40 publications

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“…Previous studies have showed that RARα is a key player in the regulatory network of cell proliferation and differentiation [35,36]. Our current data suggested that CRC cell survival, proliferation, and colony formation were decreased by RARα knockdown, and were increased by RARα overexpression, suggesting that RARα plays an important role in the progression of CRC.…”

Section: Discussionsupporting

confidence: 60%

Oncogenic retinoic acid receptor α promotes human colorectal cancer growth through simultaneously regulating p21 transcription and GSK3β/β-catenin signaling

et al. 2017

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Retinoic acid receptor α (RARα) plays important roles in the progression of several cancers such as leukemia, breast cancer, and lung cancer. In this study, we demonstrated that RARα protein was frequently overexpressed in human CRC specimens and CRC cell lines. RARα knockdown decreased cell survival, proliferation, and colony formation in vitro and tumorigenic potential in nude mice. Specifically, RARα knockdown inhibited cell cycle progression at G1 phase through upregulation of cell cycle inhibitor p21, and downregulation of cyclinD1. Furthermore, RARα was directly recruited to the p21 promoter to inhibit the expression of p21. Simultaneously, RARα contributed to the progression of CRC cells in part due to upregulation of cyclinD1 via activation of GSK3β/β-catenin pathway. Molecular mechanism studies revealed RARα interacted with GSK3β and led to decreased expression of GSK3β at ser9, followed by increased β-catenin expression. Taken together, our results signified the importance of RARα in CRC and demonstrated that RARα promotes CRC progression through suppressing p21 transcription and enhancing GSK3β/β-catenin signaling. RARα might become a potential molecular target for the treatment of CRC.

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Section: Discussionsupporting

confidence: 60%

Oncogenic retinoic acid receptor α promotes human colorectal cancer growth through simultaneously regulating p21 transcription and GSK3β/β-catenin signaling

et al. 2017

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“…The prolifer-and validated their differential expression using qRT-PCR. As shown in Figure 3E and Supplemental Table 1 (supplemental material available online with this article; doi:10.1172/JCI87880DS1), the expression levels of Cd74, Sod2, Ccl2, Bop1, Cdkn2d, and Ran mRNA, which are involved in cell-cycle regulation, survival, and proliferation (24)(25)(26)(27)(28), were decreased in NFAT5-deficient RAW 264.7 cells when compared with levels in control vector-transfected cells. In contrast, the expression levels of Dap3, Fas, Stk3, and Tiam1 mRNA, which promote apoptotic death (13,(29)(30)(31), were increased in the same cells.…”

Section: Resultsmentioning

confidence: 93%

Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis

Choi¹,

You²,

Kim³

et al. 2017

Journal of Clinical Investigation

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Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation. Transcriptomic analysis of NFAT5-deficient macrophages revealed the molecular networks defining cell survival and proliferation. Proinflammatory M1-polarizing stimuli and hypoxic conditions were responsible for enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient macrophages were more susceptible to apoptotic death. Specifically, CCL2 secretion in an NFAT5-dependent fashion bestowed apoptotic resistance to RA macrophages in vitro. Injection of recombinant CCL2 into one of the affected joints of Nfat5+/- mice increased joint destruction and macrophage infiltration, demonstrating the essential role of the NFAT5/CCL2 axis in arthritis progression in vivo. Moreover, after intra-articular injection, NFAT5-deficient macrophages were more susceptible to apoptosis and less efficient at promoting joint destruction than were NFAT5-sufficient macrophages. Thus, NFAT5 regulates macrophage survival by inducing CCL2 secretion. Our results provide evidence that NFAT5 expression in macrophages enhances chronic arthritis by conferring apoptotic resistance to activated macrophages.

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“…The MigR1 vector (Addgene) was used to transduce NB4 cells for PU.1 overexpression. The preparation of retroviruses and transduction was done as previously described [ 45 ]. Briefly, the MigR1-PU.1 vector and the envelope plasmids were co-transfected into HEK-293T cells.…”

Section: Methodsmentioning

confidence: 99%

PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation

et al. 2016

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BackgroundLong noncoding RNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been characterized as a critical factor in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells. However, the essential transcription factor for gene expression of HOTAIRM1 is still unknown.FindingsChromatin immunoprecipitation (ChIP) assays revealed that PU.1 constitutively bound to the regulatory region of HOTAIRM1. Co-expression of PU.1 led to the transactivation of the regulatory region of HOTAIRM1 in a reporter assay. Detailed analysis showed that two PU.1 motifs, which were located around +1100 bp downstream of the transcriptional start site of the HOTAIRM1 promoter, were responsible for the PU.1-dependent transactivation. The induction of HOTAIRM1 by ATRA was dependent on PU.1, and ectopic expression of PU.1 significantly up-regulated HOTAIRM1. Furthermore, low HOTAIRM1 expression was observed in APL cells, which was attributed to the reduced PU.1 expression rather than the repression by PML-RARα via the direct binding.ConclusionPU.1 directly activates the expression of HOTAIRM1 through binding to the regulatory region of HOTAIRM1 during granulocytic differentiation. The reduced PU.1 expression, rather than PML-RARα itself, results in the low expression of HOTAIRM1 in APL cells. Our findings enrich the knowledge on the regulation of lncRNAs and the underlying mechanisms of the abnormal expression of lncRNAs involved in APL.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0274-1) contains supplementary material, which is available to authorized users.

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Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells

Cited by 35 publications

References 40 publications

Oncogenic retinoic acid receptor α promotes human colorectal cancer growth through simultaneously regulating p21 transcription and GSK3β/β-catenin signaling

Oncogenic retinoic acid receptor α promotes human colorectal cancer growth through simultaneously regulating p21 transcription and GSK3β/β-catenin signaling

Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis

PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation

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