title: Epigenetic inhibition of miR-663b by long non-coding RNA HOTAIR promotes pancreatic cancer cell proliferation via up-regulation of insulin-like growth factor 2.
abstract: Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Although microRNAs are involving in the carcinogenesis and development of pancreatic cancer, little information is known regarding the role of miR-663b in pancreatic cancer. In this study, the expression of miR-663b in pancreatic cancer cells was down-regulated by hypermethylation in its putative promoter region, and overexpression of miR-663b repressed cell proliferation, invasion and migration, and induced apoptosis in pancreatic cancer cells. Bioinformatics analysis, luciferase report assay and rescue experiments showed that insulin-like growth factor 2 (IGF2) was a direct target of miR-663b. Results from clinical samples showed that the expression level of miR-663b correlated with the pathological grading, and the expression of miR-663b was down-regulated and was inversely correlated with IGF2 expression level in pancreatic cancer tissues. More importantly, the long non-coding RNA, HOX transcript antisense RNA (HOTAIR), was up-regulated in both pancreatic cancer cells and tissues, and HOTAIR suppressed the expression of miR-663b in pancreatic cancer by histone modification on H3K4me3 and H3K27me3 on miR-663b promoter. Further in vivo studies demonstrated that the stable overexpression of miR-663b or knock-down of HOTAIR inhibited tumor growth and was associated with IGF2 expression. In summary, our studies demonstrated that miR-663b is epigenetically repressed by HOTAIR and exerts its tumor-suppressive function via targeting IGF2 in pancreatic cancer.
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Huihua
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Pathology, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Tongbing
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Urology, The First People's Hospital of Changzhou, The Third Hospital Affiliated to Soochow University, Changzhou, Jiangsu, China.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C561566:HOTAIR long untranslated RNA, human; C035170:IGF2 protein, human; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
keywords: HOTAIR; IGF2; miR-663b; pancreatic cancer; tumor growth