Investigation of miRNAs that affect PI3K / AKT / mTOR signaling pathway in endometrial cancer

Endometrial cancer is a very common type of cancer among women worldwide. Irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. In this study, In silico analysis and expression levels of miR-7-5p, miR-17-5p, miR-21-5p, miR-145-5p, miR-155-5p, miR-206, miR-221-3p and miR 222-3p, which affect the PI3K/AKT/mTOR pathway, were evaluated in endometrial cancer. In this study, Grade-1 (n=16), Grade-2 (n=16) and Grade-3 (n=16), archival tissues diagnosed with endometrioid adenocarcinoma, Control-1 (n=16) secretory phase and Control-2 (n=16) proliferative phase healthy endometrial archival tissues without endometrial cancer were included. In silico analyses examined molecular interactions between miRNAs and target genes. In silico analysis identified that miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p targets PIK3R1, miR-125b-5p targets PIK3C2B, miR-145-5p targets AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 targets PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1, miR-223-3p targets PIK3C2A. miRNA expression analysis was performed by the RT-PCR method. The expressions of miR-7-5p and miR-206 were higher in Grade-1, Grade-2, and Grade-3 than in Control-1 and Control-2 (p<0.05). It was observed that miR-145-5p expression decreased in Grade-1 compared to Control-1 and Control-2, and decreased in Grade-2 and Grade-3 compared to Control-2 (p<0.05). It was determined that the expressions of miR-17-5p and miR-222-3p increased in Grade-1, Grade-2 and Grade-3 compared to Control-1 and Control-2 (p<0.05). It was determined that miR-221-3p expression increased in Grade-1 and Grade-3 compared to Control-1 and Control-2, and in Grade-2 compared to Control-1 (p<0.05). No statistically significant difference was observed between the groups in the expression levels of miR-21-5p and miR-155-5p. In conclusion; miRNAs detected to be active in the PI3K/AKT/mTOR signaling pathway in Endometrial Cancer will contribute to the development of molecular targeted treatment and diagnostic strateg.