Protein arginine methyltransferase 5 is associated with malignant phenotype and peritoneal metastasis in gastric cancer

Abstract

Abstract. Identification of novel gastric cancer (GC)-related molecules is necessary to improve management of patients with GC in both diagnostic and therapeutic aspects. The aim of the present study was to determine whether protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in the progression of GC and whether it serves as a novel diagnostic marker and therapeutic target. We conducted global expression profiling of GC cell lines and RNA interference experiments to evaluate the effect of PRMT5 expression on the phenotype of GC cells. We analysed tissues of 179 patients with GC to assess the association of PRMT5 mRNA levels with clinicopathological factors. Differential expression of PRMT5 mRNA by GC cell lines correlated positively with the levels of GEMIN2, STAT3 and TGFB3. PRMT5 knockdown reduced the proliferation, invasion and migration of a GC cell line. PRMT5 mRNA levels were significantly higher in GC tissues than the corresponding adjacent normal tissues and were independent of tumour depth, differentiation and lymph node metastasis. High PRMT5 expression was an independent risk factor of positive peritoneal lavage cytology (odds ratio 3.90, P=0.003) and decreased survival. PRMT5 enhances the malignant phenotype of GC cell lines and its expression in gastric tissues may serve as a biomarker for patient stratification and a potential target of therapy.

Tanshinone IIA suppresses gastric cancer cell proliferation and migration by downregulation of FOXM1

“…Abnormal proliferation and migration of tumor cells are crucial pathological processes involved in malignant tumors (13–16). Tumor metastasis is a complex process which includes migratory tumor cells leaving the primary tumor by invasion, disseminating throughout the body via the circulatory system, and colonizing eventually at distant organs (17).…”

DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge

“…GSK3235025 (previously known as EPZ015666) ( 36 ) was proven to be a potent, selective inhibitor of PRMT5, a PRMT responsible for catalyzing H4R3me2 and H3R8me2, being active on non-histone substrates (e.g., p53, programmed cell death 4 (PDCD4)) and acting as a transcriptional repressor. PRMT5 deregulation has been linked to tumorigenesis [122,123] and ( 36 ) showed efficacy in in vitro and in vivo models of mantle cell lymphoma (MCL) [118,124]. Compound ( 36 ) was used as a probe for the enzyme study, while the improved compound GSK3326595 (previously known as EPZ015938), has recently entered dose escalation phase of clinical trials (NCT02783300) for the treatment of solid tumors and non-Hodgkin’s lymphoma [125].…”

A novel dual‐marker expression panel for easy and accurate risk stratification of patients with gastric cancer

“…Given that, it is worth challenging to develop a dual-marker expression panel being simple and consisted of only two markers, but having a high predictive performance. Since 2014, researchers at Nagoya University discovered 15 prognostic biomarkers for gastric cancer [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. This study aimed at testing the hypothesis that a combination of molecular markers can be used to establish a dual-marker expression panel that will improve stratification of patients with gastric cancer.…”