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Inhibition of LONP1 Suppresses Pancreatic Cancer Progression Via c-Jun N-Terminal Kinase Pathway–Meditated Epithelial-Mesenchymal Transition

Liu, Can, MS*; Wang, Hai, MS*; Li, Hao, MD; Chen, Xiong, MS; Wu, Xiang, MS§; Lu, Bin, PhD; Zhang, Wenling, PhD*; Zhou, Yong, PhD; Xiao, Gary Guishan, PhD#; Gao, Ge, PhD*

doi: 10.1097/MPA.0000000000001321
Original Articles
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Objective The aim of this study was to investigate the role of LONP1 in the progression of pancreatic cancer.

Methods Lentivirus was used to silence LONP1 in PANC-1 cells. Colony formation assay, cell counting kit (CCK8) assay, cell scratch-wound assay, and transwell assay were used to assess the effects of our strategy on inhibiting cancer growth, migration, and invasion. Protein expression was detected by Western blot analysis.

Results The expression of LONP1 in pancreatic carcinoma tissues was higher than that in adjacent normal pancreatic tissues. Downregulation of LONP1 suppressed the proliferation, migration, and invasion of PANC-1 cells. Knockdown of LONP1 in PANC-1 cells inhibited epithelial-mesenchymal transition and matrix metalloprotein (MMP) 2/9 by downregulation of vimentin, snail, slug, MMP2, and MMP9 and upregulation of claudin-1. The c-Jun N-terminal kinase pathway was inactivated in LONP1 knockdown PANC-1 cells. Activation of the c-Jun N-terminal kinase pathway by anisomycin treatment significantly reversed the changes in epithelial-mesenchymal transition markers and MMP2/9 induced by ablation of LONP1 in PANC-1 cells.

Conclusions LONP1 plays a vital role in the proliferation and metastasis of pancreatic cancer, which provides a potential therapeutic target for the treatment of pancreatic cancer.

From the *Department of Laboratory Medicine, Third Xiangya Hospital, Central South University;

Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Hunan Normal University;

Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha;

§Clinical Laboratory, Hainan Provincial Hospital of Chinese Medicine, Hainan;

School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou;

Department of Physiology, Xiangya School of Medicine, Central South University, Changsha;

#School of Pharmaceutical Science, Dalian University of Technology, Creighton University Medical Center, Dalian, China.

Received for publication September 3, 2018; accepted March 28, 2019.

Address correspondence to: Ge Gao, PhD, Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, No. 172 Tongzipo Rd, Changsha, Hunan 41001, China (e-mail: ggboxy@163.com); Gary Guishan Xiao, PhD, School of Pharmaceutical Science, Dalian University of Technology, Creighton University Medical Center, G-209, West Campus, 2 Linggong Rd, Dalian, Liaoning, 116000, China (e-mail: xiao_gg@163.com).

This research was supported by the Hunan Natural Science Foundation of China (2019JJ40397, 2016JJ4053) and Hainan Natural Science Foundation of China (818MS159).

The authors declare no conflict of interest.

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