Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer

Li Yang; Lingjie Zheng; Xiaonv Xie; Junjia Luo; Jing Yu; Lihua Zhang; Wenhui Meng; Yingen Zhou; Ling Chen; Dongsheng Ouyang; Honghao Zhou; Zhirong Tan

Journal of Advanced Research (Feb 2022)

Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer

Li Yang,
Lingjie Zheng,
Xiaonv Xie,
Junjia Luo,
Jing Yu,
Lihua Zhang,
Wenhui Meng,
Yingen Zhou,
Ling Chen,
Dongsheng Ouyang,
Honghao Zhou,
Zhirong Tan

Affiliations

Li Yang: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Lingjie Zheng: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Xiaonv Xie: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Junjia Luo: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Jing Yu: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Lihua Zhang: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Wenhui Meng: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Yingen Zhou: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Ling Chen: Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, PR China
Dongsheng Ouyang: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Honghao Zhou: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China
Zhirong Tan: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, Changsha 410078, PR China; National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, Changsha, Hunan 410008, PR China; Corresponding author at: Department of Clinical Pharmacology, Xiangya Hospital, Xiangya School of Medicine, Central South University, 445, 110 Xiangya Road, Changsha, Hunan 410078, PR China.

Journal volume & issue: Vol. 36
pp. 265 – 276

Abstract

Read online

Introduction: Colorectal cancer (CRC) is a common malignant tumor with a high global incidence, metastasis rate and low cure rate. Changes in lipid metabolism-related genes can affect the occurrence and development of CRC, and may be a potential therapeutic target for CRC. Therefore, starting from lipid metabolism-related genes to find natural medicines for tumor treatment may become a new direction in CRC research. Objectives: This study aimed to investigate the effect of PLA2G16, a key gene involved in lipid metabolism, on the biological function of CRC, and whether the anti-CRC effect of GCK is related to PLA2G16. Methods: To explore the role of PLA2G16 in CRC in vitro and in vivo, we performed cell proliferation, migration, invasion and nude mice tumorigenesis assays. As for the mechanism, we designed RNA-seq analysis and verified by western blotting and immunofluorescence experiments. Subsequently, we found the anti-CRC effect of GCK is related to PLA2G16 through western blotting and rescue experiments. Results: We showed that PLA2G16 was significantly higher in CRC tissues than the adjacent normal appearing tissues, and high PLA2G16 expression correlates with unfavorable prognosis of CRC patients. Further, PLA2G16 promoted the malignant progression of CRC by inhibiting the Hippo signaling pathway determined by RNA-seq analysis, and GCK exerted anti-CRC effects by inhibiting the protein expression of PLA2G16 in vitro and in vivo. Conclusion: Our results suggested that PLA2G16 promote the malignant progression of CRC by inhibiting the Hippo signaling pathway and the anti-CRC effect of GCK is through inhibiting the protein expression of PLA2G16.

Published in Journal of Advanced Research

ISSN: 2090-1232 (Print); 2090-1224 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Science (General)
Website: http://www.journals.elsevier.com/journal-of-advanced-research/

About the journal

Abstract

Keywords