miR-199a-3p Modulates MTOR and PAK4 Pathways and Inhibits Tumor Growth in a Hepatocellular Carcinoma Transgenic Mouse Model

• Main Authors: Elisa Callegari (Author), Lucilla D'Abundo (Author), Paola Guerriero (Author), Carolina Simioni (Author), Bahaeldin K. Elamin (Author), Marta Russo (Author), Alice Cani (Author), Cristian Bassi (Author), Barbara Zagatti (Author), Luciano Giacomelli (Author), Stella Blandamura (Author), Farzaneh Moshiri (Author), Simona Ultimo (Author), Antonio Frassoldati (Author), Giuseppe Altavilla (Author), Laura Gramantieri (Author), Luca Maria Neri (Author), Silvia Sabbioni (Author), Massimo Negrini (Author)
• Format: Book
• Published: Elsevier, 2018-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Prognosis is poor, and therapeutic options are limited. MicroRNAs (miRNAs) have emerged as potential therapeutic molecules against cancer. Here, we investigated the therapeutic efficacy of miR-199a-3p, an miRNA highly expressed in normal liver and downregulated in virtually all HCCs. The therapeutic value of miR-199a-3p mimic molecules was assayed in the TG221 mouse, a transgenic model highly predisposed to the development of liver cancer. Administration of miR-199a-3p mimics in the TG221 transgenic mouse showing liver cancer led to a significant reduction of number and size of tumor nodules compared to control animals. In vivo delivery confirmed protein downregulation of the miR-199a-3p direct targets, mechanistic target of rapamycin (MTOR) and p21 activated kinase 4 (PAK4), ultimately leading to the repression of FOXM1. Remarkably, the anti-tumor activity of miR-199a-3p mimics was comparable to that obtained with sorafenib. These results suggested that miR-199a-3p may be considered a promising HCC therapeutic option.

Item Description

2162-2531
10.1016/j.omtn.2018.04.002