KIAA0495/PDAM Is Frequently Downregulated in Oligodendroglial Tumors and Its Knockdown by siRNA Induces Cisplatin Resistance in Glioma Cells
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AbstractCo-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.
All Author(s) ListPang JCS, Li KKW, Lau KM, Ng YL, Wong J, Chung NYF, Li HM, Chui YL, Lui VWY, Chen ZP, Chan DTM, Poon WS, Wang Y, Mao Y, Zhou LF, Ng HK
Journal nameBrain Pathology
Volume Number20
Issue Number6
PublisherWiley: 12 months
Pages1021 - 1032
LanguagesEnglish-United Kingdom
KeywordsBCL2L1; chromosome 1p; cisplatin resistance; KIAA0495; oligodendroglial tumors; PDAM
Web of Science Subject CategoriesClinical Neurology; CLINICAL NEUROLOGY; Neurosciences; NEUROSCIENCES; Neurosciences & Neurology; Pathology; PATHOLOGY

Last updated on 2021-15-09 at 00:15