Small Nucleolar Noncoding RNA SNORA23, Up-Regulated in Human Pancreatic Ductal Adenocarcinoma, Regulates Expression of Spectrin Repeat-Containing Nuclear Envelope 2 to Promote Growth and Metastasis of Xenograft Tumors in Mice
作者： Lin Cui , Kenji Nakano , Sumalee Obchoei , Kiyoko Setoguchi , Masaki Matsumoto
DOI: 10.1053/J.GASTRO.2017.03.050
关键词:
摘要: Background & Aims Small nucleolar noncoding RNAs (snoRNAs) regulate function of ribosomes, and specific snoRNAs are dysregulated in some cancer cells. We investigated dysregulation snoRNAs pancreatic ductal adenocarcinoma (PDAC) Methods snoRNA expression PDAC cell lines by complementary DNA microarray quantitative reverse transcription polymerase chain reaction. In (n = 133), intraductal papillary mucinous neoplasm (n = 16), cystic neoplasm-associated 1), non-tumor pancreas 8) liver 3) tissues from subjects who underwent surgical resection, levels were measured reaction compared with clinicopathologic parameters survival times determined Kaplan−Meier analysis. To examine function, cells transfected snoRNA-antisense oligonucleotides flanked amido-bridged nucleic acids, or snoRNA-expression plasmids, analyzed proliferation, colony formation, spheroid invasion assays. identify snoRNA-related factors, gene proteomic profiling immunoblot Mice given intrasplenic injections MIA PaCa2- Suit2-HLMC cells; tumor-bearing nude mice then 3 weekly an antisense against SNORA23, a H/ACA-box type snoRNA, tumor growth metastasis to liver, blood, analyzed. Results Levels SNORA23 increased accumulated at the nucleolus highly metastatic their parental detected human PDAC specimens but not tissue. level correlated grade inversely disease-free time patients. Expression invasive activity formation was inhibited knockdown. profile analyses, we found increase spectrin repeat-containing nuclear envelope 2 (SYNE2) messenger RNA protein. Knockdown SYNE2 reduced activities anchor-independent survival. Administration slowed xenograft tumors, SYNE2, dissemination, liver. Conclusions which mediates sequence-specific pseudouridylation ribosomal RNAs, be tissues, correlate patient time. increases possibly through modulation ribosome biogenesis, promote invasion, tumors mice.
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