PRMT1 expression is elevated in head and neck cancer and inhibition of protein arginine methylation by adenosine dialdehyde or PRMT1 knockdown downregulates proliferation and migration of oral cancer cells

Chuang, Chun Yi; Chang, Chien Ping; Lee, Yu Jen; Lin, Wei; Chang, Wen‐Wei; Wu, Jia Sian; Cheng, Ya Wen; Lee, Huei; Li, Chuan

doi:10.3892/or.2017.5737

Cited by 30 publications

(31 citation statements)

References 51 publications

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“…Recent reports have revealed the relationship between various cancers and PRMT1, which is overexpressed in breast cancer, bladder cancer and lung cancer [17][18][19][20].. Notably, PRMT1 was recently reported to be upregulated through miR-503 in HCC [21], and PRMT1 may promote the proliferation and metastasis of HCC cells in vitro [13].…”

Section: Discussionmentioning

confidence: 99%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although it has been widely accepted that protein arginine methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration. This study aimed to investigate the role of PRMT1 in HCC growth and metastasis. Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses. Cell proliferation, colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT, crystal violet and Boyden chamber assays. Tumour growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and recurrence; PRMT1 expression was also positively correlated with microvascular invasion (P = 0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo, as well as tumour metastasis. These phenotypes were associated with STAT3 signalling pathway activation. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. Conclusions: We revealed a significant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation. PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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“…Alteration in arginine methylation of RG/RGG-containing proteins is associated with a plethora of neurodegenerative diseases and cancers (11,13,48,63,(78)(79)(80). In line with this, PRMT1 mRNA levels are increased in several cancer cells and tumors (81)(82)(83). Moreover, PRMT1 has been shown to regulate epithelial-mesenchymal transition, cancer cell migration, and invasion, which are hallmarks of cancer progression and metastasis (84).…”

Section: Tnpo1 and Tnpo3 Suppress Cirbp Phase Separation And Stressmentioning

confidence: 91%

Nonclassical nuclear localization signals mediate nuclear import of CIRBP

Hutten

Gottschalk

Hofweber

et al. 2020

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

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The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)–rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.

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“…PRMT1 is known to promote proliferation of many cancer cell lines in vitro and in vivo , ( 16,17,20‐22 ) including hepatoma cell lines. We confirmed that PRMT1 inhibition using a small molecule inhibitor, protein arginine methyltransferase inhibitor, reduced hepatoma cell proliferation under normal conditions.…”

Section: Resultsmentioning

confidence: 99%

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

et al. 2020

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Alcohol is a well-established risk factor for hepatocellular carcinoma (HCC), but the mechanisms by which alcohol promotes liver cancer are not well understood. Studies suggest that ethanol may enhance tumor progression by increasing hepatocyte proliferation and through alcohol-induced liver inflammation. Protein arginine methyltransferase 1 (PRMT1) is the main enzyme responsible for cellular arginine methylation. Asymmetric dimethyl arginine, produced by PRMT1, is a potent inhibitor of nitric oxide synthases. PRMT1 is implicated in the development of several types of tumors and cardiovascular disease. Our previous work has shown that PRMT1 in the liver regulates hepatocyte proliferation and oxidative stress and protects from alcohol-induced liver injury. However, its role in HCC development remains controversial. In this study, we found that hepatocyte-specific PRMT1-knockout mice develop an increased number of tumors in an N-nitrosodiethylamine (DEN) alcohol model of liver tumorigenesis in mice. This effect was specific to the alcohol-related component because wild-type and knockout mice developed similar tumor numbers in the DEN model without the addition of alcohol. We found that in the presence of alcohol, the increase in tumor number was associated with increased proliferation in liver and tumor, increased WNT/β-catenin signaling, and increased inflammation. We hypothesized that increased inflammation was due to increased oxidative and nitrosative stress in knockout mice. By blocking excess nitric oxide production using an inducible nitric oxide synthase inhibitor, we reduced hepatocyte death and inflammation in the liver and prevented the increase in WNT/β-catenin signaling, proliferation, and tumor number in livers of knockout mice. Conclusion: PRMT1 is an important protection factor from alcohol-induced liver injury, inflammation, and HCC development. (Hepatology Communications 2020;4:790-808). SEE EDITORIAL ON PAGE 787H epatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. (1,2) Unlike other cancers with known risk factors, molecular mechanisms of HCC development are not completely understood. Most patients with HCC have a history of chronic liver disease and cirrhosis, (3) but cirrhosis associated with hepatitis B and C and chronic alcohol drinking account for most cases. (4) About 40% of individuals who chronically consume alcohol develop fatty liver, which can advance to alcoholic hepatitis and/or cirrhosis. Although there have been conflicting findings, currently it is accepted that

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PRMT1 expression is elevated in head and neck cancer and inhibition of protein arginine methylation by adenosine dialdehyde or PRMT1 knockdown downregulates proliferation and migration of oral cancer cells

Cited by 30 publications

References 51 publications

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Nonclassical nuclear localization signals mediate nuclear import of CIRBP

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

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