RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells.

Signal Transduction and Targeted Therapy
Xiaojuan LinXiaomin Zhong

Abstract

LIN28B is an evolutionarily conserved RNA-binding protein that regulates mRNA translation and miRNA let-7 maturation in embryonic stem cells and developing tissues. Increasing evidence demonstrates that LIN28B is activated in cancer and serves as a critical oncogene. However, the underlying molecular mechanisms of LIN28B function in tumorigenesis are still largely unknown. Here we report that LIN28B was expressed in over half of the patients with epithelial ovarian cancer who were examined (n = 584). Functional experiments demonstrated that LIN28B inhibited ovarian cancer cell apoptosis. Furthermore, we showed that the proapoptotic factor BIM played an essential role in the antiapoptotic function of LIN28B. RNA-IP microarray analysis suggested that LIN28B binds to mRNAs that are associated with the DNA damage pathway, such as AKT2, in ovarian cancer cells. By binding to AKT2 mRNA and enhancing its protein expression, LIN28B regulated FOXO3A protein phosphorylation and decreased the transcriptional level of BIM, which antagonized the antiapoptosis activity of LIN28B. Taken together, these results mechanistically linked LIN28B and the AKT2/FOXO3A/BIM axis to the apoptosis pathway. The findings may have important implications in t...Continue Reading

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Citations

Nov 13, 2019·Journal of Cellular Biochemistry·Mei TangHui Zhang
Oct 31, 2019·Biological Reviews of the Cambridge Philosophical Society·Goodwin G Jinesh, Andrew S Brohl
Oct 23, 2019·Signal Transduction and Targeted Therapy·Heng ZhengXiawei Wei
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Jun 13, 2020·Frontiers in Cell and Developmental Biology·Zied BoudhraaAnne-Marie Mes-Masson
Jul 28, 2020·Signal Transduction and Targeted Therapy·Heng ZhengXiawei Wei
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Jan 23, 2022·Journal of Translational Medicine·Jiangchun WuXiaohua Wu

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Methods Mentioned

BETA
transgenic
xenograft
RNA-immunoprecipitation
RNA-IP
PCR
nuclear translocation
transfection
flow cytometry

Software Mentioned

SAS
SPSS

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