Open AccessPRMT 9 promotes hepatocellular carcinoma invasion and metastasis via activating PI 3K/Akt/ GSK ‐3β/Snail signaling
Author(s) -
Jiang Hai,
Zhou Zhenyu,
Jin Shaowen,
Xu Kang,
Zhang Heyun,
Xu Junyang,
Sun Qing,
Wang Jie,
Xu Junyao
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13598
Subject(s) - biology , protein kinase b , cancer research , metastasis , oncogene , snail , hepatocellular carcinoma , cancer , signal transduction , cell cycle , cell , microbiology and biotechnology , biochemistry , genetics , ecology
Protein arginine methyltransferases ( PRMT ) catalyze protein arginine methylation and play an important role in many biological processes. Aberrant PRMT expression in tumor cells has been documented in several common cancer types; however, its precise contribution to hepatocellular carcinoma ( HCC ) cell invasion and metastasis is not fully understood. In this study, we identified a new oncogene, PRMT 9, whose overexpression strongly promotes HCC invasion and metastasis. PRMT 9 expression was detected more frequently in HCC tissues than in adjacent noncancerous tissues. PRMT 9 overexpression was significantly correlated with hepatitis B virus antigen ( HB sAg) status, vascular invasion, poor tumor differentiation and advanced TNM stage. Patients with higher PRMT 9 expression had a shorter survival time and higher recurrence rate. PRMT 9 expression was an independent and significant risk factor for survival after curative resection. Functional studies demonstrated that PRMT 9 increased HCC cell invasion and lung metastasis. Knocking down PRMT 9 with short hairpin RNA (sh RNA ) inhibited HCC cell invasion. Further investigations found that PRMT 9 increased cell migration and invasion through epithelial‐mesenchymal transition ( EMT ) by regulating Snail expression via activation of the PI 3K/Akt/ GSK ‐3β/Snail signaling pathway. In clinical HCC samples, PRMT 9 expression was positively associated with Snail expression and was negatively associated with E‐cadherin expression. In conclusion, our study demonstrated that PRMT 9 is an oncogene that plays an important role in HCC invasion and metastasis through EMT by regulating Snail expression via activation of the PI 3K/Akt/ GSK ‐3β/Snail signaling pathway. Thus, PRMT 9 may serve as a candidate prognostic biomarker and a potential therapeutic target.