Endoplasmic Reticulum Stress and Disease · Journal article

RPLP0 drives diffuse large B‑cell lymphoma cell proliferation through reactive oxygen species‑dependent AKT/mTOR activation and inhibition of stress‑induced autophagy

Experimental and Therapeutic Medicine · August 7, 2026

Hypothesis-Generating Why this matters to you Expert discussion

Raises a question worth testing. It does not answer one.

AI Summary

This is a mechanistic cell line study demonstrating that RPLP0 promotes DLBCL proliferation through ROS-dependent AKT/mTOR signaling and suppression of autophagy. The findings are exploratory, identify a potential signaling axis, and suggest a therapeutic hypothesis but do not establish clinical efficacy or validate a drug target.

What was studied

In vitro mechanistic study with gene expression profiling. DLBCL cell lines; genomic analysis of The Cancer Genome Atlas-DLBCL and GSE12453 datasets.. Intervention: RPLP0 overexpression or knockdown; pharmacologic modulators (N-acetylcysteine, rapamycin, 3-MA). Compared with: Control cells with baseline RPLP0 expression; cells treated with vehicle or specific inhibitors.

Key findings

RPLP0 knockdown inhibited DLBCL cell proliferation and caused G2-phase arrest without affecting apoptosis RPLP0 knockdown increased reactive oxygen species accumulation and caused mitochondrial membrane potential depolarization RPLP0 knockdown promoted autophagy-related gene 5 (ATG5) overexpression and increased autophagic vesicles

Safety

Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.

Who this may help

This work is preclinical and does not yet establish RPLP0 as a validated therapeutic target or support a change in DLBCL clinical practice. In vivo efficacy studies and clinical cohort validation would be necessary to determine clinical relevance.

Plain-language summary

Mechanistic study in cell lines demonstrating a signaling pathway without clinical outcome data, efficacy comparison, or in vivo validation; raises questions about RPLP0's therapeutic potential rather than answering them.

Study design

As stated by the source record.

MethodsDLBCL cells underwent RPLP0 overexpression or knockdown. Functional assays included reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation, and biochemical analysis. Cells were treated with N-acetylcysteine, rapamycin, or 3-MA to interrogate the ROS-AKT/mTOR-autophagy axis. Hub genes were identified via protein-protein interaction network analysis of datasets.

DesignIn vitro mechanistic study with gene expression profiling

PopulationDLBCL cell lines; genomic analysis of The Cancer Genome Atlas-DLBCL and GSE12453 datasets.

InterventionRPLP0 overexpression or knockdown; pharmacologic modulators (N-acetylcysteine, rapamycin, 3-MA)

ComparatorControl cells with baseline RPLP0 expression; cells treated with vehicle or specific inhibitors

Clinical bottom line

Caveats

Source does not report the number of cell lines, biological replicates, or statistical power for any experiment
No effect sizes, confidence intervals, or p-values reported for primary findings
In vivo xenograft or animal model data not described
Specific DLBCL cell lines used are not identified in the source text

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

limited

Cell line-based functional study without in vivo model or clinical cohort.

Directness

limited

Mechanistic pathway analysis in cultured cells; no direct evidence of clinical benefit or patient relevance.

Consistency

insufficient

Source does not report comparison with prior literature or replication across independent studies.

Risk of bias

moderate

Experimental methods described but no blinding, randomization, or control for confounding reported.

Sample adequacy

insufficient

Source does not report number of cell lines, replicates, or sample sizes for experiments.

What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.

Source abstract

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive subtype of non-Hodgkin lymphoma with poor outcomes.Identifying the primary molecular causes of DLBCL remains key.The present study examined the function of ribosomal protein lateral stalk subunit P0 (RPLP0) in DLBCL pathogenesis.The Cancer Genome Atlas-DLBCL and GSE12453 datasets overlapping differentially expressed genes were identified.Hub genes were identified via protein-protein interaction network analysis.DLBCL cells were subjected to functional tests following RPLP0 overexpression or knockdown.Reverse transcription-quantitative PCR, western blotting, flow cytometry, transmission electron microscopy, colony formation assay and biochemical analysis were among the tests performed.N-acetylcysteine (NAC), rapamycin (RAPA) and 3-MA were among the medication therapies.In the DLBCL datasets, six ribosome-associated genes were differentially expressed.RPLP0 knockdown inhibited the proliferation of DLBCL cells and caused G 2 -phase arrest, without impacting apoptosis.Thioredoxin, heat shock protein family A member 1A and heat shock protein family B member 1 expression was downregulated by RPLP0 knockdown, which also increased the NAD + /NADH ratio, promoted reactive oxygen species (ROS) accumulation and caused mitochondrial membrane potential depolarization.Meanwhile, 3-MA reversed the effects of RPLP0 knockdown, which encouraged LC3-II accumulation, autophagy-related gene 5 (ATG5) overexpression and an increase in autophagic vesicles.Autophagy-related indicators were decreased, and AKT/mTOR phosphorylation was increased by RPLP0 overexpression, which RAPA inhibited.NAC therapy preserved the viability of RPLP0-silenced cells, restored p-AKT/p-mTOR levels and restored normal LC3 and ATG5 expression.These findings suggest that RPLP0 regulates stress-induced autophagy through ROS-dependent AKT/mTOR signaling and may represent a potential therapeutic target for DLBCL.

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Endoplasmic Reticulum Stress and DiseaseBelinda HodgeJiahong TangXutao YangShanshan WangRochelle McgowanDaniel Shan