title: H19 promotes pancreatic cancer metastasis by derepressing let-7's suppression on its target HMGA2-mediated EMT.
abstract: The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.
authors.affiliation: Department of General Surgery, The Sixth People' Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chenchao
authors.initials: C
authors.lastname: Ma
authors.forename: Kate
authors.initials: K
authors.lastname: Nong
authors.forename: Hongda
authors.initials: H
authors.lastname: Zhu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Xinyu
authors.initials: X
authors.lastname: Huang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yuan
authors.forename: Kaixing
authors.initials: K
authors.lastname: Ai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C094335:H19 long non-coding RNA; D025743:HMGA2 Protein; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C487931:mirnlet7 microRNA, human