Details

Autor(en) / Beteiligte

• Ohyagi-Hara, Chifumi
• Sawada, Kenjiro
• Kamiura, Shoji
• Tomita, Yasuhiko
• Isobe, Aki
• Hashimoto, Kae
• Kinose, Yasuto
• Mabuchi, Seiji
• Hisamatsu, Takeshi
• Takahashi, Toshifumi
• Kumasawa, Keiichi
• Nagata, Shigenori
• Morishige, Ken-ichirou
• Lengyel, Ernst
• Kurachi, Hirohisa
• Kimura, Tadashi

Titel

miR-92a Inhibits Peritoneal Dissemination of Ovarian Cancer Cells by Inhibiting Integrin α5 Expression

Ist Teil von

• The American journal of pathology, 2013-05, Vol.182 (5), p.1876-1889

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.