SOX11 and HIG-2 are cross-regulated and affect growth in mantle cell lymphoma.

Authors:

Kuci V, Nordström L, Conrotto P, Ek S.

In:
Source: Leuk Lymphoma
Publication Date: (2016)
Issue: 57(8): 1883-92
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
Granta519
Species: human
Tissue Origin: blood
JeKo-1
Species: human
Tissue Origin: blood
Z-138
Species: human
Tissue Origin: blood
Platform:
4D-Nucleofectorâ„¢ X-Unit
Experiment

all cells transfected in solution SF:

Granta 519: DN-113: 85% TF

Z-138: CM-138: 86% TF

Jeko-1: DJ-105: 82% TF


Transfection of GRANTA-519, Z138, and JEKO-1 cells was carried out using the Amaxa 4D-Nucleofector (Lonza, Cologne, Germany). Briefly, 2.5 million cells were resuspended in SF solution (Lonza, Cologne, Germany) and mixed with 500 nM pool of siRNA (Sigma-Aldrich, St. Louis, MO). In each reaction, a scrambled sequence (SCR) and a GFP-producing plasmid were used as controls. Sequences of the siRNA pools, and the transfection programs used can be found in Supplemental Tables S3 and S4, respectively. Transient knock-down and overexpression of SOX11 was performed as described in Gustavsson et al.[10]

Abstract

The transcriptional factor SOX11 is a disease-defining antigen in mantle cell lymphoma (MCL) and absent in most non-malignant tissues. To explore the role of SOX11-related cell signaling, and potentially take benefit from these for targeted therapy, associated networks and proteins need to be defined. In this study, we used an inducible SOX11 knock-down system followed by gene expression analysis to identify co-regulated genes and associated signaling pathways. A limited number (n?=?27) of significantly co-regulated genes were identified, including SETMAR, HIG-2, and CD24. Further analysis confirmed co-regulation of SOX11 with HIG-2 and CD24 at the protein level. Of major interest, knock-down of HIG-2 reduced SOX11 levels and increased proliferation, the proteins are thus cross-regulated. HIG-2 was localized at the plasma cell membrane in both cell lines and primary MCL cells, and could potentially be of interest for targeted therapy.