Department of Clinical Laboratory, Guangzhou Twelfth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Hematology, Guangzhou Twelfth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Mol Biol Rep. 2023 Dec 12;51(1):10. doi: 10.1007/s11033-023-08994-1.
The Proteolipid Protein 2 (PLP2), a protein in the Endoplasmic Reticulum (ER) membrane, has been reported to be highly expressed in various tumors. Previous studies have demonstrated that the reduced PLP2 can induce apoptosis and autophagy through ER stress-related pathways, leading to a decreased proliferation and aggressiveness. However, there is no research literature on the role of PLP2 in Acute Myeloid Leukemia (AML).
PLP2 expression, clinical data, genetic mutations, and karyotype changes from GEO, TCGA, and timer2.0 databases were analyzed through the R packages. The possible functions and pathways of cells were explored through GO, KEGG, and GSEA enrichment analysis using the clusterProfiler R package. Immuno-infiltration analysis was conducted using the Cibersort algorithm and the Xcell R package. RT-PCR and western blot techniques were employed to identify the PLP2 expression, examine the knockdown effects in THP-1 cells, and assess the expression of genes associated with endoplasmic reticulum stress and apoptosis. Flow cytometry was utilized to determine the apoptosis and survival rates of different groups.
PLP2 expression was observed in different subsets of AML and other cancers. Enrichment analyses revealed that PLP2 was involved in various tumor-related biological processes, primarily apoptosis and lysosomal functions. Additionally, PLP2 expression showed a strong association with immune cell infiltration, particularly monocytes. In vitro, the knockdown of PLP2 enhanced endoplasmic reticulum stress-related apoptosis and increased drug sensitivity in THP-1 cells.
PLP2 could be a novel therapeutic target in AML, in addition, PLP2 is a potential endoplasmic reticulum stress regulatory gene in AML.
内质网（ER）膜上的蛋白脂蛋白 2（PLP2）在各种肿瘤中高度表达。先前的研究表明，减少 PLP2 通过 ER 应激相关途径诱导细胞凋亡和自噬，从而导致增殖和侵袭性降低。然而，目前尚无关于 PLP2 在急性髓系白血病（AML）中的作用的研究文献。
通过 R 包分析 GEO、TCGA 和 timer2.0 数据库中的 PLP2 表达、临床数据、遗传突变和核型变化。使用 clusterProfiler R 包通过 GO、KEGG 和 GSEA 富集分析探索细胞的可能功能和途径。使用 Cibersort 算法和 Xcell R 包进行免疫浸润分析。采用 RT-PCR 和 Western blot 技术鉴定 PLP2 表达，检测 THP-1 细胞中的敲低效果，并评估与内质网应激和细胞凋亡相关的基因表达。采用流式细胞术测定不同组的细胞凋亡率和存活率。
PLP2 在 AML 和其他癌症的不同亚群中均有表达。富集分析表明，PLP2 参与了各种与肿瘤相关的生物学过程，主要是细胞凋亡和溶酶体功能。此外，PLP2 表达与免疫细胞浸润呈强相关性，特别是单核细胞。在体外，PLP2 的敲低增强了内质网应激相关的细胞凋亡，并增加了 THP-1 细胞对药物的敏感性。
PLP2 可能是 AML 的一种新的治疗靶点，此外，PLP2 是 AML 中潜在的内质网应激调节基因。
