PRMT6 Promotes Lung Tumor Progression via the Alternate Activation of Tumor-Associated Macrophages

Avasarala, Sreedevi; Wu, Pei Ying; Khan, Samia Q.; Su, Yanlin; Scoyk, Michelle Van; Bao, Jianqiang; Lorenzo, Alessandra Di; David, Odile; Bedford, Mark T.; Gupta, Vineet; Winn, Robert A.; Bikkavilli, Rama Kamesh

doi:10.1158/1541-7786.mcr-19-0204

Cited by 43 publications

(38 citation statements)

References 48 publications

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“…including bladder, lung, and breast cancer [27,28], and its elevation is correlated with poor prognosis for patients with breast, colon, or lung cancers [4,13,29].…”

Section: Prmt6 Expression Is Upregulated In Various Human Malignanciesmentioning

confidence: 99%

“…PRMT6 is a predominantly nuclear enzyme characterized by its distinct substrates specificity and by its automethylation, which plays an important role for its stability and activity [3][4][5]. Kinetic studies have attributed a distributive rather than processive mode of action to PRMT6 in its catalysis of demethylation of targets [6].…”

Section: Introductionmentioning

confidence: 99%

“…PRMT6 expression is up-regulated in various human malignancies, including bladder, lung, and breast cancer [ 26 , 27 ], and its elevation is correlated with poor prognosis for patients with breast, colon, or lung cancers [ 4 , 13 , 28 ]. Recent data using genetically engineered mice provide compelling support for an oncogenic role for PRMT6 in mammary gland tumorigenesis, suggesting that it may be a good therapeutic target [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Licochalcone A is a natural selective inhibitor of arginine methyltransferase 6

Gong

Maegawa

Yang

et al. 2021

Biochemical Journal

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Arginine methylation is a post-translational modification that is implicated in multiple biological functions including transcriptional regulation. The expression of protein arginine methyltransferases (PRMT) has been shown to be upregulated in various cancers. PRMTs have emerged as attractive targets for the development of new cancer therapies. Here, we describe the identification of a natural compound, licochalcone A, as a novel, reversible and selective inhibitor of PRMT6. Since expression of PRMT6 is upregulated in human breast cancers and is associated with oncogenesis, we used the human breast cancer cell line system to study the effect of licochalcone A treatment on PRMT6 activity, cell viability, cell cycle, and apoptosis. We demonstrated that licochalcone A is a non-S-adenosyl L-methionine (SAM) binding site competitive inhibitor of PRMT6. In MCF-7 cells, it inhibited PRMT6-dependent methylation of histone H3 at arginine 2 (H3R2), which resulted in a significant repression of estrogen receptor activity. Licochalcone A exhibited cytotoxicity towards human MCF-7 breast cancer cells, but not MCF-10A human breast epithelial cells, by upregulating p53 expression and blocking cell cycle progression at G2/M, followed by apoptosis. Thus, licochalcone A has potential for further development as a therapeutic agent against breast cancer.

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“…including bladder, lung, and breast cancer [27,28], and its elevation is correlated with poor prognosis for patients with breast, colon, or lung cancers [4,13,29].…”

Section: Prmt6 Expression Is Upregulated In Various Human Malignanciesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Licochalcone A is a natural selective inhibitor of arginine methyltransferase 6

Gong

Maegawa

Yang

et al. 2021

Biochemical Journal

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“…(108,109). TAMs mediate lung tumor progression enhanced by protein arginine methyl transferase 6 (PRMT6) (110). Exosomes derived from TAMs enhance the tumor growth and metastasis in mice (111).…”

Section: Exosomal Mirnas Of Tams Regulate Tumor Growth and Anti-cancementioning

confidence: 99%

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

Kwon

Kim

et al. 2020

Front. Immunol.

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Tumor microenvironment consists of cancer cells and various stromal cells such as endothelial cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils, macrophages, and other innate and adaptive immune cells. Of these innate immune cells, macrophages are an extremely heterogeneous population, and display both pro-inflammatory and anti-inflammatory functions. While M1 macrophages (classically activated macrophages) display anti-tumoral and pro-inflammatory functions, M2 macrophages display pro-tumoral and anti-inflammatory functions. Cellular interactions and molecular factors in the tumor microenvironment affect the polarization of macrophages. We review molecules and immune cells that influence the polarization status of macrophages. Tumor-associated macrophages (TAMs) generally express M2 phenotype, and mediate many processes that include tumor initiation, angiogenesis, and metastasis. A high number of TAMs has been associated with the poor prognosis of cancers. MicroRNAs (miRNAs) have been known to regulate cellular interactions that involve cancer cells and macrophages. Tumor-derived exosomes play critical roles in inducing the M1 or M2-like polarization of macrophages. The roles of exosomal miRNAs from tumor cells in the polarization of macrophages are also discussed and the targets of these miRNAs are presented. We review the effects of exosomal miRNAs from TAMs on cancer cell invasion, growth, and anti-cancer drug resistance. The relevance of exosomal microRNAs (miRNAs) as targets for the development of anti-cancer drugs is discussed. We review recent progress in the development of miRNA therapeutics aimed at elevating or decreasing levels of miRNAs.

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“…Recent studies had reported that PRMT6 promotes the proliferation of endometrial cancer cells through the AKT/mTOR pathway, further promoting carcinogenesis [18]. Additionally, there were also related studies on lung cancer, hepatocellular carcinoma, colon cancer and prostate cancer [19]. Whereas, the mechanism of PRMT6 in gliomas is not precise, with insu cient immune-related studies.…”

Section: Introductionmentioning

confidence: 99%

High PRMT6 expression Associated With Prognosis and Immune Infiltration in Glioma

Yang

Wang

Long

et al. 2021

Preprint

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Background Glioma is characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, the prognosis of glioma is getting worse and worse with the increase of grade, which is not optimistic. Therefore, biological markers for glioma are needed in clinical to detect and evaluate the situation and prognosis of patients with glioma. In many studies, we have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors, which is associated with prognosis of patient. However, there has been no report or study on the role of PRMT6 in glioma. Methods In this study, we used various tumor-related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. Besides, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results PRMT6 is significantly differentially expressed in multiple tumors, which is associated with survival and prognosis. Especially in gliomas, the PRMT6 expression gradually increased with the grade increasing. Besides, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in various databases. Conclusions Our results indicate that high PRMT6 expression is a potential biomarker for predicting prognosis and progression of glioma.

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PRMT6 Promotes Lung Tumor Progression via the Alternate Activation of Tumor-Associated Macrophages

Cited by 43 publications

References 48 publications

Licochalcone A is a natural selective inhibitor of arginine methyltransferase 6

Licochalcone A is a natural selective inhibitor of arginine methyltransferase 6

Exosomal MicroRNAs as Mediators of Cellular Interactions Between Cancer Cells and Macrophages

High PRMT6 expression Associated With Prognosis and Immune Infiltration in Glioma

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