Open Access
ARTICLE
PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways
Yangmei Zhang*1, Xichang Zhou†1, Long Cheng†, Xiang Wang*, Qinglin Zhang‡, Youwei Zhang*, Sanyuan Sun*
* Department of Oncology, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, P.R. China
† Department of Intervention, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, P.R. China
‡ Department of Central Laboratory, Xuzhou Central Hospital, Xuzhou Medical University, Xuzhou, P.R. China
Oncology Research 2020, 28(3), 213-223. https://doi.org/10.3727/096504019X15668125347026
Abstract
PRKAA1 (protein kinase AMP-activated catalytic subunit 1) is a catalytic subunit of AMP-activated protein
kinase (AMPK), which plays a key role in regulating cellular energy metabolism through phosphorylation,
and genetic variations in the PRKAA1 have been found to be associated with gastric cancer risk. However, the
effect and underlying molecular mechanism of PRKAA1 on gastric cancer tumorigenesis, especially the proliferation and apoptosis, are not fully understood. Our data showed that PRKAA1 is highly expressed in BGC-
823 and MKN45 cells and is expressed low in SGC-7901 and MGC-803 cells in comparison with the other
gastric cancer cells. PRKAA1 downregulation by shRNA or treatment of AMPK inhibitor compound C significantly inhibited proliferation as well as promoted cell cycle arrest and apoptosis of BGC-823 and MKN45 cells.
Moreover, the expression of PCNA and Bcl-2 and the activity of JNK1 and Akt signaling were also reduced
in BGC-823 and MKN45 cells after PRKAA1 downregulation. In vivo experiments demonstrated that tumor
growth in nude mice was significantly inhibited after PRKAA1 silencing. Importantly, inactivation of JNK1
or Akt signaling pathway significantly inhibited PRKAA1 overexpression-induced increased cell proliferation
and decreased cell apoptosis in MGC-803 cells. In conclusion, our findings suggest that PRKAA1 increases
proliferation and restrains apoptosis of gastric cancer cells through activating JNK1 and Akt pathways.
Keywords
Cite This Article
Zhang, Y., Zhou, X., Cheng, L., Wang, X., Zhang, Q. et al. (2020). PRKAA1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells Through Activating JNK1 and Akt Pathways.
Oncology Research, 28(3), 213–223.