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

Köstü S., Bakırcı B., Şimşek E. B., Dumanlı D., Çelik A., Kaya A., ...Daha Fazla

Iranian Biomedical Journal, cilt.29, sa.6, ss.397-404, 2025 (ESCI, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 6
  • Basım Tarihi: 2025
  • Doi Numarası: 10.61882/ibj.5229
  • Dergi Adı: Iranian Biomedical Journal
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, BIOSIS, CINAHL, EMBASE, MEDLINE, Directory of Open Access Journals
  • Sayfa Sayıları: ss.397-404
  • Anahtar Kelimeler: Epigenetics, Piwi-interacting RNA, Triple negative breast neoplasms
  • Kırklareli Üniversitesi Adresli: Evet

Özet

Background: Breast cancer 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. D.