Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

Zhu, Zhiyan; Wang, Hao; Wei, Yiliang; Meng, Fanrong; Liu, Zhe; Zhang, Zhenfa

doi:10.1177/1010428317695929

Cited by 30 publications

(29 citation statements)

References 29 publications

(37 reference statements)

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“…Overexpressed PRDM16 was found to restrict ASMC oxidative stress injury, proliferation and migration, while acting to enhance apoptosis. The dysregulation of PRDM16 has been implicated in the progression of various diseases (Kinameri et al, 2008;Zhu et al, 2017). The ectopic expression of PRDM16 has been shown to promote the trans-differentiation of VSMCs into beige adipocytes, indicating that PRDM16 may regulate development of AS through VSMCs (Brown et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: PRDM16 Upregulation Induced by MicroRNA-448 Inhibition Alleviates Atherosclerosis via the TGF-β Signaling Pathway Inactivation

Liu¹,

Song²,

Ji³

et al. 2020

Front. Physiol.

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The dysregulated expression of microRNAs (miRs) has been associated with pathological and physiological processes of atherosclerosis (AS). In addition, PR domain-containing 16 (PRDM16), a transcriptional mediator of brown fat cell identity and smooth muscle cell activities, may be involved in the hypercholesterolemia during development of AS. The bioinformatic analysis identified a regulatory miR-448 of PRDM16. Hence, the current study aimed to explore whether miR-448 influenced the activities of aortic smooth muscle cell (ASMCs) in AS. We validated that miR-448 was highly expressed in peripheral blood of patients with AS and aortic smooth muscle of AS model mice. Whereas, PRDM16 was downregulated in the aortic smooth muscle of AS model mice. PRDM16 overexpression was observed to inhibit oxidative stress injury and cell proliferation, and promote apoptosis of ASMCs. Mechanistic studies revealed that miR-448 targeted PRDM16 and negatively regulated the PRDM16 expression, while PRDM16 blocked the TGF-β signaling pathway. Furthermore, Downregulated miR-448 alleviated oxidative stress injury, and attenuated ASMC cell proliferation, migration and enhanced cell apoptosis through upregulation of PRDM16. Taken together, silencing of miR-448 upregulates PRDM16 and inactivates the TGF-β signaling pathway, thereby impeding development of AS by repressing the proliferation, migration and invasion of ASMCs.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: PRDM16 Upregulation Induced by MicroRNA-448 Inhibition Alleviates Atherosclerosis via the TGF-β Signaling Pathway Inactivation

Liu¹,

Song²,

Ji³

et al. 2020

Front. Physiol.

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“…The transcriptional activity of PRDM1 is essential for the differentiation and maintenance of long-lived plasma cells 3,4 , whose downregulation has been associated with several types of cancer. Therefore, PRDM1 is considered a tumour suppressor gene 23,[43][44][45][46][47] . The two major isoforms, PRDM1α and PRDM1β, are expressed in myeloma cells, while only the PRDM1α isoform is expressed in non-tumorigenic plasma cells 11,28 .…”

Section: Discussionmentioning

confidence: 99%

Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells

Romero-Garcia

Gómez-Jaramillo

Mateos

et al. 2020

Sci Rep

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Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the accumulation of malignant plasma cells in the bone marrow. The transcription factor PRDM1 is a master regulator of plasma cell development and is considered to be an oncosuppressor in several lymphoid neoplasms. The PRDM1β isoform is an alternative promoter of the PRDM1 gene that may interfere with the normal role of the PRDM1α isoform. To explain the induction of the PRDM1β isoform in MM and to offer potential therapeutic strategies to modulate its expression, we characterized the cis regulatory elements and epigenetic status of its promoter. We observed unexpected patterns of hypermethylation and hypomethylation at the PRDM1α and PRDM1β promoters, respectively, and prominent H3K4me1 and H3K9me2 enrichment at the PRDM1β promoter in non-expressing cell lines compared to PRDM1β-expressing cell lines. After treatment with drugs that inhibit DNA methylation, we were able to modify the activity of the PRDM1β promoter but not that of the PRDM1α promoter. Epigenetic drugs may offer the ability to control the expression of the PRDM1α/PRDM1β promoters as components of novel therapeutic approaches.

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“…The TAD boundaries in pro-B cell were enriched with Nanog and PRDM1 motifs (p = 0.01). Interestingly, the coding gene of Prdm1 that is associated with various cancer developments [11,[37][38][39][41][42][43] exhibited the high expression level only in lymphoma (Additional file 2: Figure S4), even though all samples included PRDM1 in A compartment (Additional file 1: Table S5) enriched in TAD boundaries (Fig. 6a).…”

Section: Tad Boundaries Suggest Gene Regulation Function In Cancermentioning

confidence: 99%

Analyzing the 3D chromatin organization coordinating with gene expression regulation in B-cell lymphoma

2019

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Background: Eukaryotes compact chromosomes densely and non-randomly, forming three-dimensional structures. Alterations of the chromatin structures are often associated with diseases. In particular, aggressive cancer development from the disruption of the humoral immune system presents abnormal gene regulation which is accompanied by chromatin reorganizations. How the chromatin structures orchestrate the gene expression regulation is still poorly understood. Herein, we focus on chromatin dynamics in normal and abnormal B cell lymphocytes, and investigate its functional impact on the regulation of gene expression. Methods: We conducted an integrative analysis using publicly available multi-omics data that include Hi-C, RNAseq and ChIP-seq experiments with normal B cells, lymphoma and ES cells. We processed and re-analyzed the data exhaustively and combined different scales of genome structures with transcriptomic and epigenetic features. Results: We found that the chromatin organizations are highly preserved among the cells. 5.2% of genes at the specific repressive compartment in normal pro-B cells were switched to the permissive compartment in lymphoma along with increased gene expression. The genes are involved in B-cell related biological processes. Remarkably, the boundaries of topologically associating domains were not enriched by CTCF motif, but significantly enriched with Prdm1 motif that is known to be the key factor of B-cell dysfunction in aggressive lymphoma. Conclusions: This study shows evidence of a complex relationship between chromatin reorganization and gene regulation. However, an unknown mechanism may exist to restrict the structural and functional changes of genomic regions and cognate genes in a specific manner. Our findings suggest the presence of an intricate crosstalk between the higher-order chromatin structure and cancer development.

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Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

Cited by 30 publications

References 29 publications

RETRACTED: PRDM16 Upregulation Induced by MicroRNA-448 Inhibition Alleviates Atherosclerosis via the TGF-β Signaling Pathway Inactivation

RETRACTED: PRDM16 Upregulation Induced by MicroRNA-448 Inhibition Alleviates Atherosclerosis via the TGF-β Signaling Pathway Inactivation

Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells

Analyzing the 3D chromatin organization coordinating with gene expression regulation in B-cell lymphoma

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