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15-PGDH as A Therapeutic Target for Cholangiocarcinoma

Lu Yao, Chang Han and Tong Wu

Cholangiocarcinoma is a type of aggressive liver malignancy that arises from the biliary tract. Enhanced PGE2 signaling plays an important role in Cholangiocarcinoma development. Tumor suppressor gene 15-PGDH catalyzes oxidation of PGE2 and is potential target in intervention CCA progression. This notion is supported by our previous research that overexpression 15-PGDH inhibits CCA cells growth not only by decreasing PGE2 level, but also by activating PPARγ through 15-keto-PGE2. To induce 15-PGDH expression, multiple strategies are proposed based on regulatory mechanisms of 15-PGDH. In our recent published report, we provide novel evidence that ω-3 PUFA induces 15-PGDH in CCA by inhibiting miR26a/b which prevents 15-PGDH translation and support the use of ω-3 PUFA as nontoxic adjuvant therapeutic agent for the treatment of human cholangiocarcinoma.