MiR-106b promotes therapeutic antibody expression in CHO cells by targeting deubiquitinase CYLD.

Abstract

MicroRNAs (miRNAs) function as important regulators of major cellular processes, such as cell cycle, proliferation, development, and apoptosis. Recently, miRNA engineering of Chinese hamster ovary (CHO) cells has emerged as a promising strategy for enhancing therapeutic antibody production. Previously, we have reported that inhibition of deubiquitinase cylindromatosis (CYLD) remarkably enhanced the therapeutic antibody production in CHO cells. However, the mechanisms regulating CYLD in CHO cells remain elusive. Herein, we demonstrated that miR-106b targets CYLD directly, as shown by a series of bioinformatics analyses and experimental assays. Stable overexpression of miR-106b in CHO cells promoted CHO cell viability and subsequent antibody expression in transient transfection assay. Furthermore, the results in fed-batch culture showed that stable overexpression of miR-106b in a CHO-IgG cell line achieved about 0.66-fold promotion in product titer compared to the parental cells. Meanwhile, overexpression of miR-106b did not affect the quality of antibody. Taken together, our findings highlight the effect of miR-106b inhibition in CYLD synthesis and its function in antibody expression as a new target for improving CHO manufacturing cells.