title: miR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression.
abstract: Ovarian cancer is characterized by widespread peritoneal dissemination and ascites and has a cure rate of only 30%. As has been previously reported, integrin α5 plays a key role in the peritoneal dissemination of ovarian cancer. Our aim was to identify a new miRNA that regulates integrin α5 expression and analyze the therapeutic potential of targeting this miRNA. By using an IHC analysis, we proved that high integrin α5 expression correlates with a poor prognosis in Japanese patients with International Federation of Gynecology and Obstetrics stage III ovarian cancer. Based on an miRNA algorithm search, we identified hsa-mir-92a (miR-92a) as a candidate. The level of miR-92a expression was significantly inversely correlated with ITGA5 expression in various cancer cells. Transfection of precursor miR-92a reduced integrin α5 expression in ovarian cancer cells, which was accompanied by the inhibition of cancer cell adhesion, invasion, and proliferation. miR-92a overexpression reduced the luciferase activity of the ITGA5 3'-untranslated region, suggesting that ITGA5 mRNA is a direct target of miR-92a. In in vivo ovarian cancer xenografts, the enforced expression of miR-92a in HeyA-8 cells suppressed peritoneal dissemination. Although we still have a long way to go before an effective and nontoxic miRNA-based cancer therapy can be introduced into the clinic, the inhibition of integrin α5 expression by targeting miR-92a needs to be explored further for future applications in ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Chifumi
authors.initials: C
authors.lastname: Ohyagi-Hara
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sawada
authors.forename: Shoji
authors.initials: S
authors.lastname: Kamiura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Aki
authors.initials: A
authors.lastname: Isobe
authors.forename: Kae
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Kinose
authors.forename: Seiji
authors.initials: S
authors.lastname: Mabuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hisamatsu
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kumasawa
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagata
authors.forename: Ken-Ichirou
authors.initials: K
authors.lastname: Morishige
authors.forename: Ernst
authors.initials: E
authors.lastname: Lengyel
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kurachi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D011379:Prognosis; D011485:Protein Binding / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D039482:Integrin alpha5; C541874:MIRN92 microRNA, human; D035683:MicroRNAs