The modification of ferroptosis and abnormal lipometabolism through overexpression and knockdown of potential prognostic biomarker perilipin2 in gastric carcinoma
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.
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.
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.
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.
KeywordsPerilipin2 Gastric carcinoma Overexpression Knockdown Ferroptosis pathway Lipometabolism
We would like to express our gratitude to Tissue Bank and Department of Science Research Center of China-Japan Union Hospital of Jilin University.
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.
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.
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.
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