title: KIAA0495/PDAM is frequently downregulated in oligodendroglial tumors and its knockdown by siRNA induces cisplatin resistance in glioma cells.
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.
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China. jessepang@cuhk.edu.hk
authors.forename: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.forename: Kin-Mang
authors.initials: KM
authors.lastname: Lau
authors.forename: Yeung Lam
authors.initials: YL
authors.lastname: Ng
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Nellie Yuk-Fei
authors.initials: NY
authors.lastname: Chung
authors.forename: Hiu-Ming
authors.initials: HM
authors.lastname: Li
authors.forename: Yiu-Loon
authors.initials: YL
authors.lastname: Chui
authors.forename: Vivian Wai Yan
authors.initials: VW
authors.lastname: Lui
authors.forename: Zhong-ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Danny Tat-Ming
authors.initials: DT
authors.lastname: Chan
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Mao
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D062085:RNA, Long Noncoding / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013697:Thermosensing / Q000235:genetics; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C000607535:long non-coding RNA KIAA0495, human; D002945:Cisplatin