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Prp19 facilitates invasion of hepatocellular carcinoma via p38 mitogen-activated protein kinase/twist1 pathway.


ABSTRACT: Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. However, the pathological role of Prp19 in hepatocellular carcinoma (HCC) is still elusive. Here, we reported that Prp19 was increased in most HCC tissues and HCC cell lines, and its overexpression in HCC tissues was positively correlated with vascular invasion, tumor capsule breakthrough and poor prognosis. Prp19 potentiated migratory and invasive abilities of HCC cells in vitro and in vivo. Furthermore Prp19 facilitated Twist1-induced epithelial-mesenchymal transition. Mechanistic insights revealed that Prp19 directly binded with TGF-?-activated kinase1 (TAK1) and promoted the activation of p38 mitogen-activated protein kinase (MAPK), preventing Twist1 from degradation. Finally Prp19/p38 MAPK/Twist1 axis was attested in nude mice xenografts and HCC patient specimens. This work implies that the gain of Prp19 is a critical event during the progression of HCC, making it a promising target for malignancies with aberrant Prp19 expression.

SUBMITTER: Yin J 

PROVIDER: S-EPMC5008335 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Prp19 facilitates invasion of hepatocellular carcinoma via p38 mitogen-activated protein kinase/twist1 pathway.

Yin Jie J   Wang Lan L   Zhu Ji-Min JM   Yu Qian Q   Xue Ru-Yi RY   Fang Ying Y   Zhang Yi-An YA   Chen Yan-Jie YJ   Liu Tao-Tao TT   Dong Ling L   Shen Xi-Zhong XZ  

Oncotarget 20160401 16


Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. However, the pathological role of Prp19 in hepatocellular carcinoma (HCC) is still elusive. Here, we reported that Prp19 was increased in most HCC tissues and HCC cell lines, and its overexpression in HCC tissues was positively correlated with vascular invasion, tumor capsule breakthrough and poor prognosis. Prp19 potentiated migratory and invasive abilities of HCC cel  ...[more]

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