miR-24 Inhibition Increases Menin Expression and Decreases Cholangiocarcinoma Proliferation. Academic Article uri icon


  • Menin (MEN1) is a tumor-suppressor protein in neuroendocrine tissue. Therefore, we tested the novel hypothesis that menin regulates cholangiocarcinoma proliferation. Menin and miR-24 expression levels were measured in the following intrahepatic and extrahepatic cholangiocarcinoma (CCA) cell lines, Mz-ChA-1, TFK-1, SG231, CCLP, HuCCT-1, and HuH-28, as well as the nonmalignant human intrahepatic biliary line, H69. miR-24 miRNA and menin protein levels were manipulated invitro in Mz-ChA-1 cell lines. Markers of proliferation and angiogenesis (Ki-67, vascular endothelial growth factors A/C, vascular endothelial growth factor receptors 2/3, angiopoietin 1/2, and angiopoietin receptors 1/2) were evaluated. Mz-ChA-1 cells were injected into the flanks of nude mice and treated with miR-24 inhibitor or inhibitor scramble. Menin expression was decreased in advanced CCA specimens, whereas miR-24 expression was increased in CCA. Menin overexpression decreased proliferation, angiogenesis, migration, and invasion. Inhibition of miR-24 increased menin protein expression while decreasing proliferation, angiogenesis, migration, and invasion. miR-24 was shown to negatively regulate menin expression by luciferase assay. Tumor burden and expression of proliferative and angiogenic markers was decreased in the miR-24 inhibited tumor group compared to controls. Interestingly, treated tumors were more fibrotic than the control group. miR-24-dependent expression of menin may be important in the regulation of nonmalignant and CCA proliferation and may be an additional therapeutic tool for managing CCA progression.

published proceedings

  • Am J Pathol

altmetric score

  • 4.25

author list (cited authors)

  • Ehrlich, L., Hall, C., Venter, J., Dostal, D., Bernuzzi, F., Invernizzi, P., ... Glaser, S.

citation count

  • 28

complete list of authors

  • Ehrlich, Laurent||Hall, Chad||Venter, Julie||Dostal, David||Bernuzzi, Francesca||Invernizzi, Pietro||Meng, Fanyin||Trzeciakowski, Jerome P||Zhou, Tianhao||Standeford, Holly||Alpini, Gianfranco||Lairmore, Terry C||Glaser, Shannon

publication date

  • January 2017