KIAA0495/PDAM Is frequently downregulated in oligodendroglial tumors and its knockdown by siRNA induces cisplatin resistance in glioma cells

Jesse Chung Sean Pang, Kay Ka Wai Li, Kin Mang Lau, Yeung Lam Ng, John Wong, Nellie Yuk Fei Chung, Hiu Ming Li, Yiu Loon Chui, Vivian Wai Yan Lui, Zhong Ping Chen, Danny Tat Ming Chan, Wai Sang Poon, Yin Wang, Yin Mao, Liangfu Zhou, Ho Keung Ng

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Co-deletion of chromosomes 1p and 19q is a common event in oligodendroglial tumors (OTs), suggesting the presence of OT-related genes. The aim of this study was to identify the target genes residing in the minimally deleted regions on chromosome 1p36.31-p36.32 that might be involved in OTs. A novel gene KIAA0495/p53-dependent apoptosis modulator (PDAM) was found frequently deregulated, with 37 of 58 (63.8%) OTs examined showing reduced expression compared with normal brain. Chromosome 1p loss and epigenetic modifications were the major mechanisms contributing to PDAM downregulation. The role of PDAM in chemosensitivity was also evaluated. PDAM knockdown had no effect on sensitivity to vincristine, lomustine, temozolomide and paclitaxel, but could induce cisplatin resistance in glioma cells harboring wild-type p53. B-cell CCL/lymphoma 2 (BCL2)-like 1 (BCL2L1) exhibited significant upregulation, while BCL2 showed partial derepression in PDAM-silenced cells after cisplatin treatment, suggesting that alteration of anti-apoptotic genes contributed in part to cisplatin resistance. Knockdown of BCL2L1 abrogated the induced cisplatin-resistant phenotype. Moreover, our data suggested that PDAM might function as a non-protein-coding RNA. Collectively, these findings suggest that PDAM deregulation may play a role in OT development and that PDAM may possess the capacity to modulate apoptosis via regulation of p53-dependent anti-apoptotic genes.

Original languageEnglish (US)
Pages (from-to)1021-1032
Number of pages12
JournalBrain Pathology
Volume20
Issue number6
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • BCL2L1
  • chromosome 1p
  • cisplatin resistance
  • KIAA0495/PDAM
  • oligodendroglial tumors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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