Molecules and Cells

  • 제45권10호
  • /
  • Pages.718-728
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression

  • Kim, Hyungmin (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Lee, Jeehan (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Jung, Soon-Young (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Yun, Hye Hyeon (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Ko, Jeong-Heon (Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Jeong-Hwa (Department of Biochemistry, College of Medicine, The Catholic University of Korea)
  • 투고 : 2022.03.07
  • 심사 : 2022.06.07
  • 발행 : 2022.10.31
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초록

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

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과제정보

This research was funded by grants from the National Research Foundation of Korea (NRF-2019R1A2C1086949).

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