Journal Article

Reduced Proteolipid Protein 2 promotes endoplasmic reticulum stress-related apoptosis and increases drug sensitivity in acute myeloid leukemia

Xiong, Qingquan, Qu, Jia, Xie, Fahui, Feng, Kexin, Tan, Mingzhu, Liao, Haixiu, Zeng, Longhui, Lin, Dainan, Huang, Jun, Chen, Weiwen

2024

Overview

Background 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). Methods 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. Results 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. Conclusions PLP2 could be a novel therapeutic target in AML, in addition, PLP2 is a potential endoplasmic reticulum stress regulatory gene in AML.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Acute myeloid leukemia / algorithms / Animal Anatomy / Animal Biochemistry / Apoptosis / Autophagy / Biomedical and Life Sciences / drugs / Endoplasmic reticulum / Endoplasmic Reticulum - metabolism / endoplasmic reticulum stress / Endoplasmic Reticulum Stress - genetics / Flow cytometry / Histology / Humans / Infiltration / Karyotypes / karyotyping / Leukemia / Leukemia, Myeloid, Acute - drug therapy / Leukemia, Myeloid, Acute - genetics / Leukemia, Myeloid, Acute - metabolism / Life Sciences / Metastases / Monocytes / Morphology / Myelin proteolipid protein / myeloid leukemia / Original Article / Proteins / Proteolipids - genetics / Proteolipids - metabolism / Proteolipids - pharmacology / regulator genes / Therapeutic targets / therapeutics / Western blotting