Potential of circular RNA itchy E3 ubiquitin protein ligase as a biomarker and treatment target for multiple myeloma

Hui Zhou, Jie Zhang, Bihua Chen, Hengyu Liu, Xiyu Liu, Zhongyi Sun, Zhou Ouyang, Fang Zhou, Yajun Li, Junqiao He, Lijun Wang, Ruolan Zeng, Ling Xiao


Background: This study aimed to investigate the association of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) expression with disease risk, clinical characteristics, progression-free survival (PFS) and overall survival (OS) of multiple myeloma (MM), and to explore the influence of circ-ITCH overexpression on MM cell activities n vitro.
Methods: Bone marrow samples from 92 MM patients and 30 healthy controls were collected, and circ- ITCH expression was detected by quantitative polymerase chain reaction. PFS and OS in MM patients were calculated. Circ-ITCH in human MM cell lines and normal bone marrow mononuclear cells (BMMCs) were detected. Circ-ITCH overexpression and control overexpression plasmids were transfected to U226 cell line, and cell proliferation as well as apoptosis were assessed.
Results: Circ-ITCH expression was under-expressed in MM patients compared to healthy controls. And receiver operating characteristic curve displayed that circ-ITCH could distinguish MM patients from healthy controls [area under curve: 0.809 (95% CI: 0.722–0.895)]. Additionally, circ-ITCH high expression was associated with decreased International Staging System (ISS) stage in MM patients. Kaplan-Meier curves and Cox’s regression analysis displayed that circ-ITCH expression was positively correlated with PFS and OS. In vitro, circ-ITCH expression was lower in MM cell lines (including RPMI8226, U226 and NCI-H929) compared to normal BMMCs. In U226 cells, cell proliferation was decreased but apoptosis was elevated by circ-ITCH overexpression.
Conclusions: Circ-ITCH might serve as a potential biomarker and treatment target for MM.