Bayesian modeling identifies PLAG1 as a key regulator of proliferation and survival in rhabdomyosarcoma cells

Yanbin Zheng, Lin Xu, Mohammed Hassan, Xiaoyun Zhou, Qinbo Zhou, Dinesh Rakheja, Stephen X. Skapek

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We recently developed a novel computational algorithm that incorporates Bayesian methodology to identify rhabdomyosarcoma disease genes whose expression level correlates with copy-number variations, and we identified PLAG1 as a candidate oncogenic driver. Although PLAG1 has been shown to contribute to other type of cancers, its role in rhabdomyosarcoma has not been elucidated. We observed that PLAG1 mRNA is highly expressed in rhabdomyosarcoma and is associated with PLAG1 gene copynumber gain. Knockdown of PLAG1 dramatically decreased cell accumulation and induced apoptosis in rhabdomyosarcoma cells, whereas its ectopic expression increased cell accumulation in vitro and as a xenograft and promoted G1 to S-phase cell-cycle progression. We found that PLAG1 regulates IGF2 expression and influences AKT and MAPK pathways in rhabdomyosarcoma, and IGF2 partially rescues cell death triggered by PLAG1 knockdown. The expression level of PLAG1 correlated with the IC50 of rhabdomyosarcoma cells to BMS754807, an IGF receptor inhibitor.

Original languageEnglish (US)
Pages (from-to)364-374
Number of pages11
JournalMolecular Cancer Research
Volume18
Issue number3
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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