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PARP14 promotes the proliferation and gemcitabine chemoresistance of pancreatic cancer cells through activation of NF‐κB pathway
Author(s) -
Yao Na,
Chen Qiuyang,
Shi Weihai,
Tang Liming,
Fu Yue
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23011
Subject(s) - biology , poly adp ribose polymerase , carcinogenesis , cancer research , signal transduction , apoptosis , gene knockdown , cell growth , gemcitabine , microbiology and biotechnology , cancer , polymerase , biochemistry , enzyme , genetics
Pancreatic cancer (PC) is the most fatal gastrointestinal malignancy in the world, with a 5‐year relative survival of only 8%. Poly(ADP‐ribose) polymerase (PARP)14, a member of the macro‐PARP subfamily proteins, has been reported to participate in various biologic and pathologic processes in multiple cancers. The roles and underlying molecular mechanisms of PARP14 in PC carcinogenesis, however, remain to be elucidated. In this study, we for the first time discovered that PARP14 was highly expressed in human primary PC specimens and significantly correlated with poor patient prognosis. Using loss‐of‐function studies in vitro and in vivo, we showed that the knockdown of PARP14 led to enhanced apoptosis, repressed proliferation, and gemcitabine (GEM) resistance of PC cells. Further investigations revealed that PARP14 was significantly overexpressed in GEM‐resistant PC cells (SW1990/GZ). And silencing of PARP14 significantly reversed the GEM resistance of SW1990/GZ cells. To the mechanism, PARP14 could stimulate PC progression by the activation of nuclear factor‐κB (NF‐κB) signaling pathway. And inhibition of NF‐κB signal could significantly reverse PARP14–overexpression triggered PC carcinogenesis. In conclusion, PARP14 could promote PC cell proliferation, antiapoptosis, and GEM resistance via NF‐κB signaling pathway, highlighting its potential role as a therapeutic target for PC.