H19 promotes pancreatic cancer metastasis by derepressing let-7’s suppression on its target HMGA2-mediated EMT

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 nor...

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Published inTumor biology Vol. 35; no. 9; pp. 9163 - 9169
Main Authors Ma, Chenchao, Nong, Kate, Zhu, Hongda, Wang, Weiwei, Huang, Xinyu, Yuan, Zhou, Ai, Kaixing
Format Journal Article
LanguageEnglish
Published Dordrecht Springer Netherlands 01.09.2014
Springer Nature B.V
Subjects
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cancer Research
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Cell adhesion & migration
Cell Line, Tumor
Cell Movement - genetics
Epithelial-Mesenchymal Transition - genetics
Gene Expression Regulation, Neoplastic
HMGA2 Protein - genetics
HMGA2 Protein - metabolism
Humans
Metastasis
MicroRNAs - genetics
Neoplasm Invasiveness
Neoplasm Metastasis
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Research Article
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA Interference
RNA, Long Noncoding - genetics
Tumors
HMGA2
LncRNA-H19
let-7
Pancreatic cancer
Migration
Invasion
Online AccessGet full text

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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.
AbstractList 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.
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.[PUBLICATION 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.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.
Author Yuan, Zhou
Zhu, Hongda
Ai, Kaixing
Wang, Weiwei
Ma, Chenchao
Nong, Kate
Huang, Xinyu
Author_xml – sequence: 1
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  surname: Ma
  fullname: Ma, Chenchao
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  fullname: Nong, Kate
  organization: Department of General Surgery, The Sixth People’ Hospital Affiliated to Shanghai Jiaotong University
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  organization: Department of General Surgery, The Sixth People’ Hospital Affiliated to Shanghai Jiaotong University
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  organization: Department of General Surgery, The Sixth People’ Hospital Affiliated to Shanghai Jiaotong University
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  organization: Department of General Surgery, The Sixth People’ Hospital Affiliated to Shanghai Jiaotong University
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  surname: Ai
  fullname: Ai, Kaixing
  email: akxing8258@gmail.com
  organization: Department of General Surgery, The Sixth People’ Hospital Affiliated to Shanghai Jiaotong University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/24920070$$D View this record in MEDLINE/PubMed
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Issue 9
Keywords HMGA2
LncRNA-H19
let-7
Pancreatic cancer
Migration
Invasion
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PublicationSubtitle Tumor Markers, Tumor Targeting and Translational Cancer Research
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Springer Nature B.V
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Snippet 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...
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SubjectTerms Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cancer Research
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Cell adhesion & migration
Cell Line, Tumor
Cell Movement - genetics
Epithelial-Mesenchymal Transition - genetics
Gene Expression Regulation, Neoplastic
HMGA2 Protein - genetics
HMGA2 Protein - metabolism
Humans
Metastasis
MicroRNAs - genetics
Neoplasm Invasiveness
Neoplasm Metastasis
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Research Article
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA Interference
RNA, Long Noncoding - genetics
Tumors
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Title H19 promotes pancreatic cancer metastasis by derepressing let-7’s suppression on its target HMGA2-mediated EMT
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