Cell Death and Disease (Sep 2022)

LncRNA SNHG1 regulates neuroblastoma cell fate via interactions with HDAC1/2

  • Chia-Lang Hsu,
  • Chieh-Fan Yin,
  • Yi-Wen Chang,
  • Ya-Chih Fan,
  • Shih-Han Lin,
  • Yu-Ching Wu,
  • Hsuan-Cheng Huang,
  • Hsueh-Fen Juan

DOI
https://doi.org/10.1038/s41419-022-05256-z
Journal volume & issue
Vol. 13, no. 9
pp. 1 – 10

Abstract

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Abstract The small nucleolar RNA host gene 1 (SNHG1) is a novel oncogenic long non-coding RNA (lncRNA) aberrantly expressed in different tumor types. We previously found highly expressed SNHG1 was associated with poor prognosis and MYCN status in neuroblastoma (NB). However, the molecular mechanisms of SNHG1 in NB are still unclear. Here, we disrupted endogenous SNHG1 in the MYCN-amplified NB cell line SK-N-BE(2)C using the CRISPR/Cas9 system and demonstrated the proliferation and colony formation ability of SNHG1-knowndown cells were suppressed. The transcriptome analysis and functional assays of SNHG1-knockdown cells revealed SNHG1 was involved in various biological processes including cell growth, migration, apoptosis, cell cycle, and reactive oxygen species (ROS). Interestingly, the expression of core regulatory circuitry (CRC) transcription factors in MYCN-amplified NB, including PHOX2B, HAND2, GATA3, ISL1, TBX1, and MYCN, were decreased in SNHG1-knockdown cells. The chromatin-immunoprecipitation sequencing (ChIP-seq) and transposase-accessible chromatin using sequencing (ATAC-seq) analyses showed that chromatin status of these CRC members was altered, which might stem from interactions between SNHG1 and HDAC1/2. These findings demonstrate that SNHG1 plays a crucial role in maintaining NB identity via chromatin regulation and reveal the function of the lncRNA SNHG1 in NB.