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Long Non-coding RNA H19 Recruits NFYB to Activate MBTD1 and Regulate Doxorubicin Resistance in Lymphoma Cells

Lili Feng1, Qinying Yan2, Xiaofang Xu3

  • 1Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China.

Molecular Biotechnology
|November 26, 2022
PubMed

Insights

This study reveals how the H19 long non-coding RNA promotes doxorubicin (DOX) resistance in lymphoma by activating MBTD1 expression via NFYB. Targeting this H19/NFYB/MBTD1 axis may overcome drug resistance in lymphoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Doxorubicin (DOX) is a key chemotherapy for lymphoma.
  • Drug resistance to DOX significantly hinders treatment efficacy.
  • Understanding resistance mechanisms is crucial for improving lymphoma therapy.

Purpose of the Study:

  • To investigate the role of the H19/NFYB/MBTD1 axis in DOX resistance in lymphoma cells.
  • To elucidate the molecular mechanisms underlying this interaction.
  • To identify potential therapeutic targets for overcoming DOX resistance.

Main Methods:

  • Bioinformatics analysis for gene correlation and pathway prediction.
  • Cell culture of DOX-resistant lymphoma cell lines (OCI-Ly8/DOX, SU-DHL-2/DOX).
  • Gene silencing (siRNA), luciferase reporter assays, ChIP-qPCR, in vitro and in vivo experiments.

Main Results:

  • MBTD1 expression is elevated in lymphoma, correlating with advanced stage and DOX resistance.
  • MBTD1 silencing reduced DOX resistance in lymphoma cells.
  • H19 recruits NFYB to activate MBTD1 transcription, promoting DOX resistance and cell growth.
  • Silencing H19 inhibited DOX-resistant cell growth in vitro and in vivo.

Conclusions:

  • The H19/NFYB/MBTD1 axis plays a critical role in promoting DOX resistance in lymphoma.
  • H19 upregulates MBTD1 via NFYB-dependent transcriptional activation.
  • This axis represents a potential therapeutic target for overcoming DOX resistance in lymphoma.
Keywords:
DoxorubicinDrug resistanceLong non-coding RNA H19LymphomaMBTD1NFYB

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