Expression and function of B-cell lymphoma/leukemia-2 interacting protein 2 in prostate cancer
CHEN Yuanjie
YU Tianyi
LI Zixiang
LI Wang
Abstract：Objective To explore the expression of B-cell lymphoma/leukemia 2 interacting protein 2(BNIP2)in prostate cancer tissues and its impact on cancer cell invasion and migration.Methods Expression levels of BNIP2 in prostate cancer tissues and adjacent tissues were detected using immunohistochemistry and quantitative reverse transcription polymerase chain reaction.Relationship of BNIP2 expression with the clinicopathological characteristics and prognosis of prostate cancer was analyzed.After overexpressing the BNIP2 gene in prostate cancer PC3 cells via plasmid transfection,we assessed cell proliferation viability using the Cell Counting Kit-8 assay,measured the apoptosis rate by TUNEL assay,evaluated the number of migrating and invading cells with a Transwell assay,and detected the expression levels of apoptosis and epithelial-mesenchymal transition-related proteins by Western blot.Results The mRNA relative expression level of BNIP2 in prostate cancer tissues(0.428±0.318)and its protein-positive expression rate(50.0%,15/30)were significantly lower than those in adjacent tissues(1.000±0.523;80.0%,24/30).The integrated optical density of the protein was markedly reduced(cancer tissues:0.296±0.063;adjacent tissues:1.000±0.112),with all differences being statistically significant(t=5.093,P<0.001;χ2=4.821,P=0.028;t=31.270,P<0.001).Positive expression of BNIP2 showed a moderate negative correlation with more advanced TNM staging,higher Gleason scores,and more progressive T staging,while also exhibiting a significant negative correlation with distant metastasis and lymph node metastasis.Specifically,the proportion of patients with Gleason scores≤7 was significantly higher in the positive group than in the negative group(86.7%vs.46.7%,P=0.017),the proportion of T1-T2 staging was higher(80.0%vs.40.0%,P=0.025),and all patients in the positive group were free of distant metastasis(100.0%vs.73.3%,P=0.042).Additionally,the lymph node metastasis rate was lower in the positive group(N0:86.7%vs.53.3%,P=0.049),and the proportion of early-stage(Ⅰ-Ⅱ)patients was higher(80.0%vs.33.3%,P=0.010).The median biochemical recurrence-free survival of patients with positive BNIP2 expression was not reached,superior to the 24.0 months observed in those with negative expression(Log-rank χ2=5.124,P=0.048).In functional experiments,overexpression of BNIP2 significantly inhibited the proliferation,migration,and invasion of PC3 cells while promoting apoptosis.Conclusion BNIP2 expression is downregulated in prostate cancer and is associated with favorable pathological features and longer patient survival.Its overexpression promotes apoptosis and suppresses tumor proliferation,migration,and invasion.These findings suggest that BNIP2 holds significant potential as a tumor suppressor gene,prognostic biomarker,and therapeutic target.
Keywords：Prostate cancerB-cell lymphoma/leukemia 2 interacting protein 2Clinical pathological characteristicsPrognosis
Publication Date：2025-07-28
Online Publishing Date：2025-10-17(First online date of this platform, not the publication date of the document)
Pages：6( 652-657 )