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Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells

Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells

Published on: April 25, 2018

Long intergenic non-protein coding RNA 1949 suppresses rituximab resistance in diffuse large B-cell lymphoma via

Shusen Lin¹, Shenrong Mo¹, Hongyao Chen¹

¹Hematology and Oncology Department, No. 924 Hospital of PLA Joint Logistic Support Force Guilin, Guangxi, China.

American Journal of Translational Research

|October 20, 2025

Abstract

Objective:

To investigate the role of long non-coding RNA LINC01949 in mediating rituximab sensitivity and its underlying epigenetic mechanisms.

Methods:

Expression of LINC01949 was analyzed in rituximab-sensitive and -resistant diffuse large B-cell lymphoma (DLBCL) cell lines using Gene Expression Omnibus datasets. Functional assays involved LINC01949 knockdown in sensitive cells and overexpression in resistant cells, followed by evaluation of drug response (IC50, apoptosis) and protein levels. Mechanistic studies examined H3K27me3 modification and one cut homeobox 2(ONECUT2) expression. Rescue experiments employed H3K27me3 demethylase inhibitor (GSK-J4) and ONECUT2 inhibitor (CSRM617). EZH2 binding to LINC01949 was assessed by RIP-qPCR.

Results:

LINC01949 expression was significantly downregulated in rituximab-resistant cells. Its knockdown in sensitive cells conferred resistance, while overexpression in resistant cells restored sensitivity. Mechanistically, LINC01949 loss reduced H3K27me3 levels, leading to derepression of the oncogenic transcription factor ONECUT2. Pharmacological restoration of H3K27me3 or inhibition of ONECUT2 reversed resistance. RIP-qPCR confirmed direct binding of LINC01949 to EZH2, which was diminished in resistant cells.

Conclusion:

LINC01949 suppresses rituximab resistance in DLBCL by promoting H3K27me3-dependent silencing of ONECUT2. These findings highlight the LINC01949-H3K27me3-ONECUT2 axis as a key epigenetic pathway and suggest potential targets to overcome resistance in DLBCL.

Keywords:

H3K27me3 Long intergenic non-protein coding RNA 1949 diffuse large B-cell lymphoma one cut homeobox 2

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