LncRNA HCG11 regulates selinexor sensitivity in multiple myeloma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Multiple myeloma (MM) is a fatal plasma cell malignancy characterized by drug resistance and relapse.
• Selinexor, targeting exportin-1 (XPO1), is a novel MM therapeutic, but response mechanisms remain unclear.
• Identifying factors influencing selinexor efficacy is crucial for improving MM patient outcomes.

Purpose of the Study:

• To investigate the role of long noncoding RNA HLA complex Group 11 (HCG11) in MM cell growth and selinexor sensitivity.
• To elucidate the molecular mechanisms by which HCG11 affects MM response to selinexor.

Main Methods:

• Quantification of HCG11 expression in MM cell lines and primary patient samples.
• Assessment of MM cell sensitivity to selinexor following HCG11 knockdown (HCG11-KD).
• Investigation of HCG11 interaction with XPO1 mRNA and its effect on XPO1 expression.
• In vivo efficacy study of HCG11-KD MM in a xenograft mouse model.

Main Results:

• High HCG11 expression in MM correlates with poorer patient survival.
• HCG11-KD significantly increases MM cell sensitivity to selinexor-induced apoptosis.
• HCG11 binds to XPO1 mRNA, enhancing its stability and translation, leading to reduced XPO1 levels upon HCG11 knockdown.
• HCG11-KD MM xenografts exhibit enhanced sensitivity to selinexor in vivo.

Conclusions:

• lncRNA HCG11 plays a critical role in regulating MM cell proliferation and resistance to selinexor.
• HCG11 promotes XPO1 expression, contributing to selinexor resistance in MM.
• Targeting HCG11 represents a potential strategy to overcome selinexor resistance in multiple myeloma.