Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells

Gou, Qing; He, Shujiao; Zhou, Zikang

doi:10.1177/1010428317691419

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…Finally, cryptotanshinone, a STAT3 inhibitor, suppressed HCC growth and migration through inhibiting STAT3 phosphorylation, which was activated by PRMT1 overexpression. Previous studies indicated that PRMT1 overexpression led to the progression and metastasis of various cancers and predicted a worse prognosis in patients [10,12,13]. Furthermore, Nakai, et al reported that EGFR methylation and activity were significantly reduced in PRMT1 knockdown cells compared to the triple-negative breast cancer parental cells [9].…”

Section: Discussionmentioning

confidence: 99%

“…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]. However, these reports did not provide enough evidence, such as in vivo experiments, to prove this role of PRMT1 and the underlying mechanism in HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, in oesophageal squamous cell carcinoma, PRMT1 activates Hedgehog signalling and upregulates the expression of target genes downstream of Hedgehog signalling to promote the growth and migration of esophageal squamous cell carcinoma (ESCC) cells [12]. One study preliminarily explored the molecular mechanisms of PRMT1 in HCC in vitro [13], but the clinicopathological significance of PRMT1 and HCC patient prognosis and the underlying mechanisms of PRMT1 in the promotion of HCC growth and metastasis in vitro and in vivo have not been examined.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…This correlates which the findings of Gou et al who found an upregulation of PRMT1 in several liver cancer cells as well as in HCC tissue. Furthermore, the authors have shown that knockdown of PRMT1 reverses EMT in HCC cell lines underlining the important role between PRMT1 and EMT and proliferation [21]. The downregulation of KDM4C which we have found in untreated HepG2 cells is also an important finding since it has diverse targets in oncogenic or tumor suppressor functions [22].…”

Section: Discussionmentioning

confidence: 67%

Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity

Ruoß

Damm

Vosough

et al. 2019

IJMS

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Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards ‘normal’ liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.

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“…Cancer Metastasis is overexpressed in melanoma; silencing PRMT1 significantly suppresses tumor growth and metastatic ability by targeting activated leukocyte cell adhesion molecule (ALCAM) [105]. Similarly, downregulation of PRMT1 inhibits cell migration and invasion in HCC and oral squamous cell carcinoma (OSCC) [106,107]. Because of complex alternative splicing in the 5′ region of its pre-mRNA, there are seven distinct PRMT1 isoforms [108].…”

Section: Arginine Methylationmentioning

confidence: 99%

The Landscape of Histone Modification in Cancer Metastasis

Qiu¹,

Wang²,

Wu³

2018

Cancer Metastasis

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Metastasis represents one of the most devastating aspects of cancer. Epithelial to mesenchymal transition (EMT) has been shown to play a critical role in tumorigenic metastasis. During metastatic progression, both genetic and epigenetic modifications endow cancer cells with properties that modulate the capacity for metastatic success. Histone modification is profoundly altered in cancer cells and contributes to cancer metastasis by controlling different metastatic phenotypes. Here, we first review histone modifications and discuss their roles in EMT and metastasis, with a particular focus on histone methylation and acetylation. Second, we review the major histone modification enzymes that control chromatin in cancer metastasis. Third, we discuss the transcriptional regulation concerted by these enzymes with EMT transcription factors at different molecular layers. Finally, we discuss pharmacologic manipulation of histone modification enzymes for metastasis treatment. A comprehensive understanding of histone modification in metastasis will not only provide new insights into our knowledge of cancer progression and metastasis, but also offer a novel approach for the development of innovative therapeutic strategies.

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Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells

Cited by 10 publications

References 20 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

Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity

The Landscape of Histone Modification in Cancer Metastasis

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