BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Multiple myeloma (MM) is an incurable plasma cell cancer.
• Chromosome instability (CIN) is a hallmark of MM, contributing to disease progression and treatment resistance.
• BUB1B expression is linked to poor outcomes in MM.

Purpose of the Study:

• To investigate the role of BUB1B and a novel circular RNA, circBUB1B_544aa, in multiple myeloma.
• To explore their impact on chromosome instability, proliferation, and drug resistance.
• To evaluate their potential as therapeutic targets.

Main Methods:

• Analysis of BUB1B and circBUB1B_544aa expression in MM patients.
• In vitro and in vivo studies of BUB1B and circBUB1B_544aa overexpression and genetic targeting.
• Mechanistic studies involving BUB1B phosphorylation of CEP170.
• Evaluation of siRNA targeting the kinase catalytic center.

Main Results:

• BUB1B expression is significantly increased in MM patients and correlates with poor prognosis.
• Overexpression of BUB1B promotes MM cell proliferation and drug resistance.
• circBUB1B_544aa is elevated in MM, synergizes with BUB1B to induce CIN, and is secreted by MM cells.
• Targeting BUB1B and circBUB1B_544aa with siRNA inhibits MM progression.

Conclusions:

• BUB1B and circBUB1B_544aa are key drivers of MM malignancy through CIN.
• Both molecules represent promising prognostic biomarkers and therapeutic targets for multiple myeloma.