Work

NPC2 deficiency as a potential target drives malignancy and chemo-resistance in DLBCL

Year: 2026

Type: article

Abstract: BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) remains challenging to treat, with a considerable proportion of patients exhibiting chemo-resistance and poor prognosis. A deeper understanding of the molecular mechanisms underlying lymphoma progression and therapy failure is urgently needed. METHODS: Using bioinformatic analysis of single-cell RNA-seq datasets, we identified NPC2 as a potential target associated with poor outcomes. Its function was explored in SU-DHL-4 and SU-DHL-2 cells by shRNA-mediated knockdown, followed by in vitro and in vivo experiments including qPCR, functional assays, flow cytometry, and xenograft models in NOD‑SCID mice. RESULTS: Low NPC2 expression was correlated with worse prognosis in DLBCL patients. NPC2 depletion did not affect cell proliferation, cell cycle, or apoptosis, but induced mitochondrial dysfunction, ROS accumulation, and enhanced migration and invasion. Importantly, NPC2 knockdown conferred resistance to vincristine both in vitro and in vivo, and promoted distant tissue damage in mouse models. CONCLUSIONS: Our study identifies NPC2 as a key regulator of DLBCL aggressiveness and chemo-resistance by modulating mitochondrial function and cell motility. NPC2 may serve as a novel potential therapeutic target for improving DLBCL treatment.

Source: Biology Direct

DOI: 10.1186/s13062-026-00833-0

Authors: Yining Yuan, Qiqi Wu, Xinyu Li, Peipei Xu

Institutions: Nanjing Drum Tower Hospital, Nanjing University, Nanjing University of Chinese Medicine

Language: English

Topic: Lymphoma Diagnosis and Treatment

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,890