MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma.
Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo. Dual-luciferase reporter assays revealed that miR-424 directly targets DCLK1 and downregulates its expression. Transfection of ES-2 cells with miR-424 mimics downregulated DCLK1 and suppressed the effects of DCLK1 overexpression on upregulating matrix metalloprotease-9 and promoting epithelial-mesenchymal transition (EMT). Taken together, these data demonstrate that miR-424 has the capacity to suppress cell invasion and EMT in OCCC by downregulating DCLK1, suggesting potential therapeutic targets and strategies for the treatment of this disease.
Department of Gynecology, The Obstetrics and Gynecology Hospital of the Fudan University, Shanghai 200011, China.
Xin
X
Wu
Department of Gynecology, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Yuanyuan
Y
Ruan
Department of Gynecology, The Obstetrics and Gynecology Hospital of the Fudan University, Shanghai 200011, China. Electronic address: jianghua@fudan.edu.cn.
Hua
H
Jiang
Department of Gynecology, The Obstetrics and Gynecology Hospital of the Fudan University, Shanghai 200011, China. Electronic address: xucj@hotmail.com.
Congjian
C
Xu
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000089742:Doublecortin-Like Kinases; D015536:Down-Regulation / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D018227:Sarcoma, Clear Cell / Q000235:genetics / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
DCLK1; EMT; Invasion; Migration; Ovarian clear cell carcinoma; miR-424