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Applied Microbiology and Biotechnology

, Volume 103, Issue 17, pp 7085–7095 | Cite as

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

  • Changzhi Xu
  • Qianqian Han
  • Qin Zhou
  • Lanlan Zhang
  • Pengfei Wu
  • Yafang Lu
  • Yan Si
  • Tengfei Ma
  • Bingbing Ma
  • Buchang ZhangEmail author
Applied genetics and molecular biotechnology
  • 93 Downloads

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.

Keywords

miR-106b CYLD CHO cells Therapeutic antibody Cell engineering 

Notes

Funding information

This work was supported by the National Natural Science Foundation of China (Grants 31600749), the Initial Foundation of Doctoral Scientific Research in Anhui University (Y01001487), the Key Research and Development Projects in Anhui Province (1704a07020075), and the project in Biotechnical Research Centre for Anhui Tianxiang Cereals, Oils and Food stuffs Co., Ltd., Anhui University (Y06159202).

Compliance with ethical standards

Competing interests

The authors declare that they have no conflicts of interest.

Ethical standards

This study does not involve any human participants or animals.

Supplementary material

253_2019_10000_MOESM1_ESM.pdf (118 kb)
ESM 1 (PDF 117 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Changzhi Xu
    • 1
  • Qianqian Han
    • 1
  • Qin Zhou
    • 1
  • Lanlan Zhang
    • 1
  • Pengfei Wu
    • 1
  • Yafang Lu
    • 1
  • Yan Si
    • 1
  • Tengfei Ma
    • 2
  • Bingbing Ma
    • 2
  • Buchang Zhang
    • 1
    Email author
  1. 1.Institutes of Physical Science and Information TechnologyAnhui UniversityHefeiPeople’s Republic of China
  2. 2.Biotechnical Research Centre for Anhui Tianxiang Cereals, Oils and Food stuffs Co., LtdAnhui UniversityHefeiPeople’s Republic of China

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