title: Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) is the sixth most common cancer in females worldwide and, although advances have been made in the detection, diagnosis and therapies for EOC, it remains the most lethal gynecologic malignancy in advanced countries. Nevertheless, relatively little is known concerning the molecular events that lead to the development of this highly aggressive disease. Elucidating the molecular mechanism involved in this disease may prove useful to understand the pathogenesis and progression of the disease, and to identify new targets for effective therapies. In the present study, we examined the role of ARK5 in ovarian cancer and normal matched tissues using western blot analysis and migration and invasion, and wound‑healing assays. The results showed that ARK5 was upregulated in ovarian cancer tissues, compared with adjacent normal tissues. Moreover, it promoted epithelial‑mesenchymal transition (EMT) and inhibited miR-1181 expression in ovarian cancer cells. Subsequent investigations showed that miR-1181 promoted mesenchymal-epithelial transition (MET) in ovarian cancer cells. Downstream target genes of miR-1181 were searched, and it was identified that miR-1181 degraded HOXA10 by targeting its 3' untranslated region (3'UTR) in ovarian cancer cells. The results confirmed that HOXA10 promoted EMT in ovarian cancer cells. Thus, activation of the ARK5/miR-1181/HOXA10 axis may be positively associated with EMT in ovarian cancer.
authors.affiliation: Gynaecology Ward-1, Linyi City People's Hospital, Shandong 276003, P.R. China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Lab, Linyi City People's Hospital, Shandong 276003, P.R. China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Li
authors.affiliation: Gastrointestinal Surgery, Linyi City People's Hospital, Shandong 276003, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.affiliation: Gynaecology Ward-3, Linyi City People's Hospital, Shandong 276003, P.R. China.
authors.forename: Su-Rong
authors.initials: SR
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
chemical_list: D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C000608024:MIRN-1181 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C069634:HOXA10 protein, human; D011494:Protein Kinases; C470845:NUAK1 protein, human