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

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.

• Authors: Xiaoying Sun, Shaojuan Yang, Xuechao Feng, Yaowu Zheng, Jinsong Zhou, Hai Wang, Yucheng Zhang, Hongyan Sun, Chengyan He
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 23 Issue 2 Pg. 241-259 (03 2020) ISSN: 1436-3305 [Electronic] Japan
• PMID: 31520166 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• PLIN2 protein, human
• Perilipin-2

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics)
• Cell Proliferation
• Female
• Ferroptosis (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Lipid Metabolism (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Perilipin-2 (antagonists & inhibitors, genetics, metabolism)
• RNA-Seq
• Stomach Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays