Transcriptional Control of PI3K/AKT/mTOR by piRNA-651 in Breast Carcinoma

Authors
Sena Köstü 1
Baturalp Bakirci 1
Ece Bilge Şimşek 1
Defne Dumanli 1
Ahmetcan Çelik 1
Alara Kaya 1
Damla Kolcuoğlu 2
Ertuğrul Çolak 3
Çağrı Öner 2
1 Kırklareli University, Faculty of Medicine, Kırklareli, TURKEY
2 Kırklareli University, Faculty of Medicine, Department of Medical Biology, Kırklareli, TURKEY
3 Eskişehir Osmangazi University, Faculty of Medicine, Department of Biostatistics, Eskişehir, TURKEY
10.66224/ibj.5229
Abstract
Background: Breast cancer (BC) is among the most prevalent malignancies in women worldwide, yet early diagnosis is associated with a high survival rate. The proliferation of BC is linked to the overexpression of genes within the PI3K/AKT/mTOR signaling pathway. piR-651 has been reported to be effective in the proliferation and metastasis of BC. This research sought to evaluate the impact of piR-651 inhibition on the PI3K/AKT/mTOR pathway in HUVEC, MCF-7, and MDA-MB-231 cells.

Methods: Anti-piR-651 and non-target sequences were introduced into HUVEC, MCF-7, and MDA-MB-231 BC cells by lipofectamine transfection. After 48 hours, total RNA was extracted, and qRT-PCR assessed the gene expression of PI3K, AKT, and mTOR.

Results: Anti-piR-651 treatment significantly increased PI3K, AKT, and mTOR gene expression in HUVECs (p < 0.001). In contrast, PI3K and mTOR expression decreased in MCF-7 and MDA-MB-231 cells (p < 0.001), while AKT expression remained unchanged in MDA-MB-231 cells (p > 0.05). Correlations between these genes varied by cell type, with significant associations observed at p < 0.05 or p < 0.01, depending on the group.

Conclusion: piR-651 inhibition causes AKT to behave independently of PI3K and mTOR, particularly in MCF-7 cells, suggesting limited gene therapy potential for estrogen receptor-positive BC. Preliminary data indicate that piR-651 inhibition may reduce BC cell proliferation through effects on PI3K and mTOR.
Keywords
Epigenetics
Piwi-interacting RNA
Triple Negative breast neoplasms
Iranian Biomedical Journal
Volume 29, Issue 6 - Serial Number 121
November and December 2025
Pages 397-404