PRMT1 regulates tumor growth and metastasis of human melanoma via targeting ALCAM

Abstract

Hepatocellular carcinoma (HCC) is a major type of liver cancer caused by the hepatitis B and C viruses, alcohol and exposure to aflatoxin. For HCC treatment, anticancer drugs have been widely used, but drug resistance in advanced HCC is an important problem, resulting in a continuous need for novel therapeutic targets. Therefore, in this study, we established a screening pipeline based on RNA-seq to screen novel therapeutic/prognostic targets in HCC and identified PRMT1 (Protein Arginine Methyltransferase 1). In the prognostic analysis, the overexpression of PRMT1 was clearly associated with poor prognosis in a number of HCC patient cohorts. Moreover, after PRMT1 knockdown, HCC cell lines exhibited cell growth and spheroid formation suppression, an increase in Sub-G1 cells by FACS analysis, and enrichment of the cell cycle pathway via functional enrichment analysis. With these results, we demonstrated that PRMT1 could be a novel prognostic marker and therapeutic target for HCC therapy.

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

“…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].…”

“…Currently, due to the close relationship between protein arginine methylation and various types of tumours, an increasing number of researchers have begun to study the relationship between PRMTs and cancer, especially PRMT1. PRMT1 regulates tumour growth and metastasis in human melanoma via targeting ALCAM [10]. In triple-negative breast cancer, PRMT1 is critical for epidermal growth factor receptor (EGFR) activity, and inhibiting PRMT1 may be an effective therapeutic strategy for overcoming intrinsic cetuximab resistance in triplenegative breast cancer cells [11].…”

FAM98A associates with DDX1-C14orf166-FAM98B in a novel complex involved in colorectal cancer progression

“…An estimated 1,361,000 people are diagnosed with CRC every year; approximately 694,000 people die from CRC annually; and 3,544,000 individuals are living with Recent studies have linked this modification to carcinogenesis and metastasis. Alterations to the PRMTs sequences have not been found so far; however, over expression of these enzymes is very often associated with the progression of various cancers [6,7]. Among PRMT family proteins, PRMT1 is crucial for the majority (approximately 85%) of methylated arginine in mammalian cells [4].…”

Global analysis of protein arginine methylation

“…Although it has taken 50 years to acknowledge the significance of PRMTs in cancer, the pace at which major discoveries have been made in recent years is phenomenal. Disruption of ADMA modification at key substrates decreases the metastatic and proliferative ability of cancer cells (Li et al, 2016), suggesting that PRMT inhibitors may be an effective strategy to combat different types of cancer. Several PRMT inhibitors have entered or are on the verge of entering the clinic, but how they alter global protein ArgMet levels remains to be uncovered.…”