Silencing of lncRNA HOTAIR enhances doxorubicin sensitivity and induces apoptosis in diffuse large B-cell lymphoma cells.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy characterized by a poor prognosis, mainly caused by late diagnosis and the absence of effective treatment options. Malignant transformation of B-cells emphasizes the necessity of novel biomarkers for early diagnosis and prognosis. Dysregulation of long non-coding RNAs (lncRNAs), fundamental regulators in biological pathways, is linked to the development of different cancer types, including DLBCL. In this study, we assessed lncRNA HOTAIR expression in DLBCL and its association with clinicopathological features while investigating the HOTAIR knockdown effects on DLBCL cell lines. RNA extraction, cDNA synthesis, and qRT-PCR were performed on tumor tissue samples from DLBCL patients and non-tumorous lymph nodes. HOTAIR knockdown was performed using short hairpin RNAs (shRNA) integrated into pmiRZip vectors, transfected into SU-DHL6 and OCI-LY10 cells through lentivirus. Then, cells were treated with doxorubicin to determine the effect of HOTAIR on drug sensitivity via apoptosis and cell cycle assays. The expression of HOTAIR was upregulated in DLBCL samples (p = 0.0001) and showed diagnostic potential with an area under the curve (AUC) of 0.85. No significant correlation was found between patients' clinicopathological characteristics and HOTAIR expression levels. HOTAIR knockdown induced apoptosis by a 34-40 % increase in cell death and led to G2 phase arrest, enhancing sensitivity to doxorubicin in HOTAIR-knocked down cells. Targeting HOTAIR may improve treatment outcomes by promoting apoptosis and enhancing doxorubicin sensitivity in DLBCL cells.