'Investigation of miRNAs That Affect the PI3K/AKT/mTOR Signaling Pathway in Endometrial Cancer'.

Abstract

Endometrial cancer is a prevalent type of cancer among women worldwide. The irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. MicroRNAs are small noncoding RNAs that play crucial roles in the pathogenesis of different cancer types. MicroRNAs target many key components of the PI3K/AKT/mTOR pathway in human tumors. In this study the PI3K/AKT/mTOR pathway was affected in endometrial cancer, and the expression levels of miR-7, miR-17, miR-145, miR-155, miR-206, miR-221, miR-222 were determined. In addition, in silico analyses were examine the molecular interactions between miRNAs and target genes. Identifying dysregulated miRNA expression in endometrial cancer is important for developing miRNA-based therapeutic strategies. In our study, Grade 1 (n = 16), Grade 2 (n = 16), Grade 3 (n = 16), tissues diagnosed with endometrioid adeno carcinoma, control 1 (n = 16) secretory phase and control 2 (n = 16) proliferative phase healthy endometrial tissues without endometrial cancer were included. miRNA expression analysis was performed using the real-time PCR. In our study, the expression of miR-7-5p, miR-145-5p, and miR-206 decreased, whereas the expression of miR-17-5p, miR-221-3p, and miR-222-3p increased in endometrial cancer (p < 0,05). Statistically significant results were not obtained to for the expression levels of miR-21-5p and miR-155-5p. miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p target PIK3R1, miR-145-5p target AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 target PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1 as identified via in silico analysis. These results can shed light on the development of molecular-targeted therapy strategies. Treatment strategies can be developed by designing ASOs, LNAs, miRNA antagomirs, or miRNA sponges for upregulated miR-17-5p, miR-221-3p, and miR-222-3p, and miRNA mimics for downregulated miR-7-5p, miR-145-5p, and miR-206.