miR-145 expression enhances integrin expression in SK-GT-4 cell line by down-regulating c-Myc expression
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Mathieu Francois Derouet1, Eugenia Dakpo1, Licun Wu1, Guan Zehong1, James Conner4, Shaf Keshavjee1,2, Marc de Perrot1,2, Thomas Waddell1,2, Elena Elimova3, Jonathan Yeung1,2 and Gail Elizabeth Darling1,2
1Latner Thoracic Surgery Research Laboratories, Princess Margaret Cancer Research Tower, University Health Network, Toronto, Ontario, Canada
2Department of Surgery, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
3Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
4Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Mathieu Francois Derouet, email: [email protected]
Gail Elizabeth Darling, email: [email protected]
Keywords: esophageal adenocarcinoma; miR-145; c-Myc; integrins; metastasis
Abbreviations: CLL: Chronic Lymphocytic Leukemia; EAC: Esophageal Adenocarcinoma; FCS: Foetal Calf Serum; HRP: Horseradish Peroxidase; PVDF: Polyvinylidene
Received: June 07, 2017 Accepted: February 21, 2018 Epub: March 08, 2018 Published: March 16, 2018
Adenocarcinoma of the esophagus is increasing in frequency and is the 6th most common cause of cancer death in North America. In adenocarcinoma cell lines, we have previously demonstrated that expression of miR-145, leads to enhanced invasion, resistance to anoikis and better attachment to fibronectin in esophageal adenocarcinoma. In contrast, expression of miR-145 acts as a tumor suppressor in squamous cell carcinoma. The molecular mechanisms responsible for the oncogenic effects of miR-145 were investigated. In this report, we demonstrate that we can partially recreate the miR-145 effects in EAC by knock down of the expression of c-Myc, which is one of the targets of miR-145. Knocking down of c-Myc expression resulted in upregulation of integrin subunits α5 and β3. Finally, we demonstrated that integrin α5 expression correlates to fibronectin attachment potential whereas integrin β3 expression correlates with resistance to anoikis and invasion potential. Finally, we demonstrate that expression of miR-145 in esophageal adenocarcinoma cell line (SK-GT-4) enhances tumor growth and metastasis in a NOD/SCID xenograft model. Overall, the oncogenic potential of miR-145 in EAC appears to be mediated by downregulation of c-Myc leading to the expression of integrins subunits α5 and β3.
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