内质网蛋白驻留受体2蛋白对胰腺癌恶性生长的影响及机制研究

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Abstract Objective： To investigate the effect of KDELR2 on the malignant growth of pancreatic cancer cells, and its underlying molecular mechanisms. Methods： The expression of KDELR2 mRNA in pan-cancer and human pancreatic cancer tissues was analyzed by UCSC XENA database, and the association of its expression with clinicopathological characteristics and prognosis of pancreatic cancer patients was analyzed based on TCGA database. GO and KEGG analyses were used to explore the potential enriched signaling pathways of KDELR2related differentially expressed genes (DEGs). qRT-PCR and Western blotting were respectively applied to detect the KDELR2 mRNA and protein expression levels in different pancreatic cancer cell lines (BXPC-3, MIA PaCa-2, PANC-1, and PaTu 8988-T), as well as normal HPNE, and the KDELR2 protein level of human pancreatic cancer tissues and paracancerous tissues were also tested. Stable pancreatic cancer cells (PaTu 8988-T and PANC-1) containing the lentiviral particles encoding KDELR2 cDNA or KDELR2 shRNA and their scramble control lentiviral particles (“KDELR2-OE” and “Vec”, “shKDELR2S1/S2”and “shNC”) were formed. In addition, CCK-8, EdU staining, Transwell, and cell colony formation experiments were applied to observe the functional change of those stable cell lines. The mitochondrial function of PaTu 8988-T and PANC-1 cells after KDELR2 knockdown was observed by JC-1, MitoSOX and DCFH-DA staining assays and ATP level detection assays respectively. Furthermore, the effect of KDELR2 shRNA on the growth of PANC-1 cells in vivo was explored by constructing a subcutaneous xenograft tumor model in nude mice. Results： KDELR2 was overexpressed in human pancreatic cancer tissues and cells, and its overexpression was positively correlated with higher tumor clinicopathological stages, indicating a poor prognosis of pancreatic cancer patients. GO function and KEGG enrichment analysis suggested that KDELR2 may regulate the growth of pancreatic cancer cells by regulating cellular energy metabolism. After silencing of KDELR2, the growth, proliferation and migration of pancreatic cancer cells were significantly inhibited. Ectopic overexpression of KDELR2 significantly promoted the proliferation and migration of pancreatic cancer cells. After KDELR2 knockdown, pancreatic cancer cells showed a significant decrease in mitochondrial membrane potential and ATP levels, a significant increase in reactive oxygen species levels (all P<0.05). A subcutaneous xenograft model in nude mice demonstrated that KDELR2 knockdown significantly inhibited the growth of PANC-1 cells in vivo. Conclusion： KDELR2 is overexpressed in pancreatic cancer tissues and correlated with poor prognosis of pancreatic cancer patients, and KDELR2 may be involved in regulating mitochondrial function and energy metabolism in cancer cells.

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Received: 30 November 2023

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	WANG Shuhang1
	WU Xiaoyang2

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WANG Shuhang1,WU Xiaoyang2. Effect of KDEL endoplasmic reticulum protein retension receptor 2 on the malignant growth of pancreatic cancer and potential mechanisms[J]. Journal of Jiangsu University(Medicine Edition), 2024, 34(02): 118-131.

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http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2024/V34/I02/118

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