Targeting PLA2G16, a Lipid Metabolism Gene, by Ginsenoside Compound K to Suppress the Malignant Progression of Colorectal Cancer

Overview

Journal J Adv Res

Specialties General Medicine
Science

Date 2022 Feb 7

PMID 35127176

Authors

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

Soon will be listed here.

Abstract

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 , 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 and .

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.

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References

Yang L, Zou H, Gao Y, Luo J, Xie X, Meng W . Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities. Drug Metab Rev. 2020; 52(1):125-138. DOI: 10.1080/03602532.2020.1714645. View

Pakiet A, Kobiela J, Stepnowski P, Sledzinski T, Mika A . Changes in lipids composition and metabolism in colorectal cancer: a review. Lipids Health Dis. 2019; 18(1):29. PMC: 6347819. DOI: 10.1186/s12944-019-0977-8. View

Wada K, Itoga K, Okano T, Yonemura S, Sasaki H . Hippo pathway regulation by cell morphology and stress fibers. Development. 2011; 138(18):3907-14. DOI: 10.1242/dev.070987. View

Brooks Robey R, Weisz J, Kuemmerle N, Salzberg A, Berg A, Brown D . Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?. Carcinogenesis. 2015; 36 Suppl 1:S203-31. PMC: 4565609. DOI: 10.1093/carcin/bgv037. View

Li L, Liang S, Wasylishen A, Zhang Y, Yang X, Zhou B . PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway. Oncotarget. 2016; 7(14):18021-35. PMC: 4951268. DOI: 10.18632/oncotarget.7694. View

Zheng M, Xin Y, Li Y, Xu F, Xi X, Guo H . Ginsenosides: A Potential Neuroprotective Agent. Biomed Res Int. 2018; 2018:8174345. PMC: 5964429. DOI: 10.1155/2018/8174345. View

Sanitioso R, Kunda Z, Fong G . Motivated recruitment of autobiographical memories. J Pers Soc Psychol. 1990; 59(2):229-41. DOI: 10.1037//0022-3514.59.2.229. View

Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C . Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018; 30(1):1-12. PMC: 5842223. DOI: 10.21147/j.issn.1000-9604.2018.01.01. View

Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez J, Zhou D . Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell. 2011; 144(5):782-95. PMC: 3237196. DOI: 10.1016/j.cell.2011.02.031. View

10.

Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y . Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2017; 23(1):1-34. PMC: 5809573. DOI: 10.1007/s10147-017-1101-6. View

11.

Li W, Zhang M, Gu J, Meng Z, Zhao L, Zheng Y . Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis. Fitoterapia. 2011; 83(1):192-8. DOI: 10.1016/j.fitote.2011.10.011. View

12.

Nazarenko I, Kristiansen G, Fonfara S, Guenther R, Gieseler C, Kemmner W . H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation of mitogenic signaling. Am J Pathol. 2006; 169(4):1427-39. PMC: 1698850. DOI: 10.2353/ajpath.2006.051341. View

13.

Jin Z, Qiu W, Liu H, Jiang X, Wang L . Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine. Chin J Nat Med. 2018; 16(2):143-149. DOI: 10.1016/S1875-5364(18)30041-4. View

14.

Lee C, Ryan E, Doherty G . Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol. 2014; 20(14):3751-61. PMC: 3983434. DOI: 10.3748/wjg.v20.i14.3751. View

15.

Sun Y, Liu Y, Chen K . Roles and mechanisms of ginsenoside in cardiovascular diseases: progress and perspectives. Sci China Life Sci. 2016; 59(3):292-8. DOI: 10.1007/s11427-016-5007-8. View

16.

Wierzbicki P, Rybarczyk A . The Hippo pathway in colorectal cancer. Folia Histochem Cytobiol. 2015; 53(2):105-19. DOI: 10.5603/FHC.a2015.0015. View

17.

Liu T, Peng F, Yu J, Tan Z, Rao T, Chen Y . LC-MS-based lipid profile in colorectal cancer patients: TAGs are the main disturbed lipid markers of colorectal cancer progression. Anal Bioanal Chem. 2019; 411(20):5079-5088. DOI: 10.1007/s00216-019-01872-5. View

18.

Dekker E, Tanis P, Vleugels J, Kasi P, Wallace M . Colorectal cancer. Lancet. 2019; 394(10207):1467-1480. DOI: 10.1016/S0140-6736(19)32319-0. View

19.

He D, Sun J, Zhu X, Nian S, Liu J . Compound K increases type I procollagen level and decreases matrix metalloproteinase-1 activity and level in ultraviolet-A-irradiated fibroblasts. J Formos Med Assoc. 2011; 110(3):153-60. DOI: 10.1016/S0929-6646(11)60025-9. View

20.

Kahn K, Adams J, Weeks J, Chrischilles E, Schrag D, Ayanian J . Adjuvant chemotherapy use and adverse events among older patients with stage III colon cancer. JAMA. 2010; 303(11):1037-45. PMC: 2893553. DOI: 10.1001/jama.2010.272. View