The PRMT1 gene expression pattern in colon cancer

Mathioudaki, Konstantina; Παπαδοκωστοπούλου, Αλεξάνδρα; Scorilas, Andreas; Xynopoulos, Dimitris; Agnanti, Niki; Talieri, Maroulio

doi:10.1038/sj.bjc.6604807

Cited by 116 publications

(115 citation statements)

References 36 publications

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“…A number of proteins responsible for a specific histone modification have been identified and extensively studied for their involvement in cancer and disease development. 12 Abnormal PRMT1 expression is found in colon and bladder cancers, 48,49 and its correspondent H4 Arg3 methylation could be used to predict recurrence of prostate cancer. 50 The specific role of PRMT1 in hematopoiesis has also been investigated.…”

Section: Discussionmentioning

confidence: 99%

PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential

Shia

Okumura

Yan

et al. 2012

Blood

103

100

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Fusion protein AML1-ETO, resulting from t(8;21) translocation, is highly related to leukemia development. It has been reported that full-length AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. We have previously shown that the expression of AE9a, a splice isoform of AML1-ETO, can rapidly cause leukemia in mice. To understand how AML1-ETO is involved in leukemia development, we took advantage of our AE9a leukemia model and sought to identify its interacting proteins from primary leukemic cells. Here, we report the discovery of a novel AE9a binding partner PRMT1 (protein arginine methyltransferase 1). PRMT1 not only interacts with but also weakly methylates arginine 142 of AE9a. Knockdown of PRMT1 affects expression of a specific group of AE9a-activated genes. We also show that AE9a recruits PRMT1 to promoters of AE9a-activated genes, resulting in enrichment of H4 arginine 3 methylation, H3 Lys9/14 acetylation, and transcription activation. More importantly, knockdown of PRMT1 suppresses the self-renewal capability of AE9a, suggesting a potential role of PRMT1 in regulating leukemia development. (Blood. 2012;119(21):4953-4962) IntroductionAcute myeloid leukemia (AML) is closely associated with chromosomal abnormalities. 1 The AML1 gene (also known as CBFA2, PEBP2␣B, and RUNX1) was initially identified as a target of chromosomal translocation in t(8;21), which is associated with 15% of de novo AML cases and Յ 40% in the AML subtype M2 of the French-American-British classification. 2,3 This specific translocation at t(8;21) involves the AML1 gene on chromosome 21 and the ETO (also known as MTG8) gene on chromosome 8 and generates an AML1-ETO fusion transcription factor. 4 AML1-ETO inherits the DNA binding RUNT domain from AML1 and is functionally characterized as a transcription factor for both gene repression and activation. 3,[5][6][7] It has been shown that AML1-ETO negatively regulates AML1 target genes, possibly through interaction with corepressor proteins such as mSin3A, N-CoR/SMRT (nuclear receptor corepressor/silencing mediator for retinoic acid receptor and thyroid hormone receptor), and HDACs (histone deacetylases). [8][9][10] AML1-ETO could also act as a transactivator on certain genes. One of the possible mechanisms is by recruiting histone modifiers to make chromatin structure more accessible to the transcription activation machinery, resulting in gene activation. A recent finding shows that p300 binds to NHR1 domain of AML1-ETO to facilitate transcription. 11 A variety of posttranslational modifications, including acetylation, methylation, and phosphorylation, on specific residues of histones and their corresponding enzymes has been discovered. 12 It is well documented that a specific histone modification on a promoter could determine the state of transcription. Specifically, methylation on histone H4 arginine 3 (Arg3) by PRMT1 (protein arginine methyltransferase 1) generally correlates with transcription activation. 13 PRMT1 is the most predominant arginine ...

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Section: Discussionmentioning

confidence: 99%

PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential

Shia

Okumura

Yan

et al. 2012

Blood

103

100

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“…PRMT1 is highly expressed in acute myeloid and lymphoid leukemia, as well as in solid tumors (17,18). Therefore, PRMT1-mediated MK blockage may contribute to leukemogenesis.…”

Section: Discussionmentioning

confidence: 99%

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

Jin

Song

et al. 2018

Exp Ther Med

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Abstract. Protein arginine methyltransferase 1 (PRMT1) serves pivotal roles in various cellular processes. However, its role in megakaryocytic differentiation has not been clearly reported. The aim of the present study was to explore the role of the PRMT-RNA binding motif protein 15 (RBM15) axis in human MK differentiation and the feasibility of targeting PRMT1 for leukemia treatment. In the present study, PRMT1 was overexpressed and the RBM15 protein was knocked down in human umbilical cord blood cluster of differentiation (CD)34 + cells and the cells were then cultured in megakaryocytic differentiation medium. Flow cytometry was used to analyze CD41 and CD42 double-positive cells, as well as the protein expression levels of PRMT1 and RBM15. The results demonstrated that human cord blood CD34 + cells differentiate into mature MKs in high thrombopoitin medium, as demonstrated by CD41 and CD42 expression. Overexpression of PRMT1 in human umbilical cord blood CD34 + cells blocked the maturation of megakaryocytic cells. Knockdown of RBM15 by short hairpin RNA produced less mature MKs. PRMT1 inhibitor rescued PRMT1-blocked megakaryocytic differentiation. These results provide evidence for a novel role of PRMT1 in the negative regulation of megakaryocytic differentiation. PRMT1 may be a therapeutic target for leukemia treatment.

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“…The loss of PRMT1 increased the levels of MMA and SDMA, and PRMT1 is transported between the nucleus and cytoplasm depending on the methylation status of substrate proteins in several cells [21]. On the other hand, PRTM1 has some splicing variants, and the noncoding variant of PRMT1, PRMT1 variant 2, was reported to be associated with progression of both colon and breast cancer [13,22]. Moreover, it was reported that PRMT1 functions such as substrate recognition and methylation are inhibited by phosphorylation of Tyr291 [23].…”

Section: Discussionmentioning

confidence: 99%

“…In several cancers, PRMT1 overexpression is related to disease progression and prognosis [12][13][14]. Moreover, some studies reported that PRMT1 was associated with the inhibition of proliferation and apoptosis induction in lung cancer and gliomas [15,16].…”

Section: Introductionmentioning

confidence: 99%

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

et al. 2015

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Background Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. Methods We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. Results PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. Conclusion Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

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The PRMT1 gene expression pattern in colon cancer

Cited by 116 publications

References 36 publications

PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential

PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential

PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord blood CD34+ cells

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

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