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The modification of ferroptosis and abnormal lipometabolism through overexpression and knockdown of potential prognostic biomarker perilipin2 in gastric carcinoma

  • Xiaoying SunEmail author
  • Shaojuan Yang
  • Xuechao Feng
  • Yaowu Zheng
  • Jinsong Zhou
  • Hai Wang
  • Yucheng Zhang
  • Hongyan Sun
  • Chengyan HeEmail author
Original Article

Abstract

Background

To investigate the biological relationship, mechanism between perilipin2 and the occurrence, advancement of gastric carcinoma, and explore the mechanism of lipid metabolism disorder leading to gastric neoplasm, and propose that perilipin2 is presumably considered as a potential molecular biomarker of gastric carcinoma.

Methods

RNA-seq was applied to analyze perilipin2 and differentially expressed genes modulated by perilipin2 in neoplastic tissues of both perilipin2 overexpression and knockdown groups in vivo. The mechanism was discovered and confirmed by Rt-qPCR, immunoblotting, immunohistochemistry, staining and microassay, respectively. Cellular function experiments were performed by flow cytometry, CCK8, clonogenic assay, etc.

Results

Overexpression and knockdown of perilipin2 augmented the proliferation and apoptosis of gastric carcinoma cell lines SGC7901 and MGC803, respectively. The neoplastic cells with perilipin2-overexpression obtained more conspicuously rapid growth than knockdown group in vivo, and perilipin2 affected the proliferation and apoptosis of gastric carcinoma cells by modulating the related genes:acyl-coa synthetase long-chain family member 3, arachidonate 15-lipoxygenase, microtubule associated protein 1 light chain 3 alpha, pr/set domain 11 and importin 7 that were participated in Ferroptosis pathway. Moreover, RNA-seq indicated perilipin2 was an indispensable gene and protein in the suppression of Ferroptosis caused by abnormal lipometabolism in gastric carcinoma.

Conclusion

Our study expounded the facilitation of perilipin2 in regulating the proliferation and apoptosis of gastric carcinoma cells by modification in Ferroptosis pathway, and we interpreted that the mechanism of gastric neoplasm caused by obesity, we also discovered that pr/set domain 11 and importin 7 are novel transcription factors relevant to gastric carcinoma. Furthermore, perilipin2 probably serves not only as a diagnostic biomarker, but also a new therapeutic target.

Keywords

Perilipin2 Gastric carcinoma Overexpression Knockdown Ferroptosis pathway Lipometabolism 

Notes

Acknowledgements

We would like to express our gratitude to Tissue Bank and Department of Science Research Center of China-Japan Union Hospital of Jilin University.

Author contributions

CYH and YWZ designed the experiments. XYS, SJY, XCF performed the experiments, XYS wrote the manuscript. HW, JSZ, HYS and YCZ checked the manuscript. All authors read and approved the final manuscript.

Funding

The study was supported by National Natural Science Foundation of China (81572082), Science and Technology Development Project of Jilin Province (20140311092YY), and Jilin Provincial Science and Technology Agency Project (2011713, 20150414015GH and 20150101153JC), Industrial Technology Research and Development (2019CO49-6).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethics standards

The animal studies were implemented in accordance with the stipulations of Laboratory Animal Welfare Ethics Committee at Jilin University (Certificate of Approval NO. pzpx201809290244). All institutional and national guidelines for the care and use of laboratory animals were followed.

Human rights statement and informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.

Supplementary material

10120_2019_1004_MOESM1_ESM.docx (297 kb)
Supplementary file1 (DOCX 297 kb)

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Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

Authors and Affiliations

  • Xiaoying Sun
    • 1
    • 2
    Email author
  • Shaojuan Yang
    • 2
    • 3
  • Xuechao Feng
    • 4
  • Yaowu Zheng
    • 4
    • 5
  • Jinsong Zhou
    • 1
    • 2
  • Hai Wang
    • 1
    • 2
  • Yucheng Zhang
    • 2
    • 6
  • Hongyan Sun
    • 2
    • 7
  • Chengyan He
    • 1
    • 2
    Email author
  1. 1.Department of Laboratory MedicineChina-Japan Union Hospital of Jilin UniversityChangchunChina
  2. 2.Norman Bethune Health Science Center of Jilin UniversityChangchunChina
  3. 3.Department of PathologyChina-Japan Union Hospital of Jilin UniversityChangchunChina
  4. 4.College of Life SciencesNortheast Normal UniversityChangchunChina
  5. 5.Institute of Cardiovascular ResearchUniversity of CaliforniaSan FranciscoUSA
  6. 6.Department of Science Research CenterChina-Japan Union Hospital of Jilin UniversityChangchunChina
  7. 7.Department of Tissue BankChina-Japan Union Hospital of Jilin UniversityChangchunChina

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