PRDM1, a Tumor‐Suppressor Gene, is Induced by Genkwadaphnin in Human Colon Cancer SW620 Cells

Kang, Hyun‐Soo; Lee, Ha‐Reum; Jee, Da Jung; Shin, Su‐Hyun; Nah, Seong‐Su; Yoon, Sun Young; Kim, Jae Wha

doi:10.1002/jcb.25262

Cited by 18 publications

(15 citation statements)

References 35 publications

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“…These observations led us to consider an alternative explanation for the maintenance of myeloma cells: Rather than an increase in proliferation, expression of the PRDM1β isoform may inhibit apoptosis. However, some contradictory results were obtained in other studies in which PRDM1α altered the proliferation of HCT116 41 and SW620 47 cells but not RKO colon cancer cells 48 , and ectopic expression of PRDM1 in a chicken fibroblast cell line inhibited cell proliferation 49 . Depending on the cellular context, further studies on the mechanisms of action of the PRDM1 isoforms will be important for understanding their roles in the regulation of apoptosis, cell proliferation and the cell cycle.…”

Section: Discussionmentioning

confidence: 90%

“…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%

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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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Section: Discussionmentioning

confidence: 90%

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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“…For instance, the silencing of the cofactor PATZ1 of KLF4 inhibits the colon cancer cell proliferation 38 . The cofactors PRDM1, EGR1, and TOPORS were shown to be tumor suppressors in colon cancer, leukemia, and lung cancer, respectively 39–41 . In addition, certain cofactors were verified to have prognostic functions in cancer.…”

Section: Resultsmentioning

confidence: 99%

Prognostic cancer gene signatures share common regulatory motifs

Wang

Goodison

et al. 2017

Sci Rep

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Scientists have discovered various prognostic gene signatures (GSs) in different cancer types. Surprisingly, although different GSs from the same cancer type can be used to measure similar biological characteristics, often rarely is there a gene shared by different GSs. To explain such a paradox, we hypothesized that GSs from the same cancer type may be regulated by common regulatory motifs. To test this hypothesis, we carried out a comprehensive motif analysis on the prognostic GSs from five cancer types. We demonstrated that GSs from individual cancer type as well as across cancer types share regulatory motifs. We also observed that transcription factors that likely bind to these shared motifs have prognostic functions in cancers. Moreover, 75% of the predicted cofactors of these transcription factors may have cancer-related functions and some cofactors even have prognostic functions. In addition, there exist common microRNAs that regulate different GSs from individual cancer types and across cancer types, several of which are prognostic biomarkers for the corresponding cancer types. Our study suggested the existence of common regulatory mechanisms shared by GSs from individual cancer types and across cancer types, which shed light on the discovery of new prognostic GSs in cancers and the understanding of the regulatory mechanisms of cancers.

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“…Two previous studies of the role of PRDM1 in cell proliferation in HCT116 and SW620 colon cancer cells draw different, contradictory conclusions (22,25). PRDM1 loss of function in these studies was based on knockdown technology in which residual PRDM1 expression could still remain if PRDM1 is maintained at a low level in RKO cells (SI Appendix, Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study has shown that PRDM1 is activated by specific polymorphic variants of p53 in RKO colon cancer cells (24). Also a recent study showed that PRDM1can inhibit SW620 colon cancer cell proliferation by inhibiting c-Myc (25). The mechanisms by which PRDM1 acts on human colon cells is incompletely understood and may lead to insights relevant to colon cancer and normal intestinal stem cell maintenance.…”

mentioning

confidence: 99%

PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids

Liu

Banister

Weige

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes. Finally, we show that forced expression of PRDM1 in human colon cancer organoids prevents the formation and growth of colon tumor organoids in vitro. These results suggest that p53 may exert tumor-suppressive effects in part through a PRDM1-dependent silencing of stem cell genes, depleting the size of the normal intestinal stem cell compartment in response to DNA damage.

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PRDM1, a Tumor‐Suppressor Gene, is Induced by Genkwadaphnin in Human Colon Cancer SW620 Cells

Cited by 18 publications

References 35 publications

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

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

Prognostic cancer gene signatures share common regulatory motifs

PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids

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