title: miR326 maturation is crucial for VEGF-C-driven cortactin expression and esophageal cancer progression.
abstract: Esophageal cancer is an aggressive human malignancy with increasing incidence in the developed world. VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here, we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive properties of esophageal squamous cell carcinoma in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR326, thereby relieving the suppressive effect of miR326 on CTTN expression. Clinically, expression of Dicer and miR326 correlated with poor prognosis in patients with esophageal cancer. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which has potential implications for the development of new biomarkers or therapies in this setting.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Chih-Chen
authors.initials: CC
authors.lastname: Hong
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan. The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pai-Sheng
authors.initials: PS
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. The PhD. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan. The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jean
authors.initials: J
authors.lastname: Chiou
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Chiu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.affiliation: The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. The Genomics Research Center, Academia Sinica, Taipei, Taiwan. Graduate Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chang
authors.affiliation: Divisions of Pulmonary and Critical Care Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yang-Hao
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Shine-Gwo
authors.initials: SG
authors.lastname: Shiah
authors.affiliation: Division of Thoracic Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Nan-Yung
authors.initials: NY
authors.lastname: Hsu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. Department of Biotechnology, Asia University, Taichung, Taiwan. Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan. Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan. jlsu@nhri.org.tw.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
mesh_terms: D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051356:Cortactin; C545322:MIRN326 microRNA, human; D035683:MicroRNAs; D042582:Vascular Endothelial Growth Factor C