Silencing of lncRNA UCA1 Reverses Doxorubicin Resistance of Breast Cancer Through Inhibiting PI3K/AKT/mTOR Signaling Pathway

Suicmez M., Namalir G., Konuş M., Ozdil H.

ChemistrySelect, cilt.9, sa.20, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 9 Sayı: 20
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/slct.202400819
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: breast cancer, doxorubicin, MCF-7, silencing, UCA1
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

The role of silencing of long non coding RNA UCA1 gene in the development of resistance to doxorubicin in breast cancer was employed. We initially induced resistance to doxorubicin in MCF-7 cells, reaching a level of 0.64 μM. Next, we employed the cytotoxicity test to assess the progression of doxorubicin resistance in both sensitive cells (MCF-7/S) and the resistant cells (MCF-7/Dox). IC50 values of MCF-7/S and MCF-7/Dox were determined as 1.65 μM and 128.5 μM, respectively. Then, UCA1 siRNA was transfected to MCF-7/Dox and MCF-7/S cells by lipofectamine method. After that, the expression levels of AKT1, PTEN, AKT2 and mTOR genes, which are involved in the PI3K/AKT/mTOR signaling pathway, were analyzed by qPCR. Finally, it was determined that the mRNA level of the UCA1 gene suppressed by siRNA was significantly decreased in MCF-7/S and MCF-7/Dox cells, except PTEN, compared to the control groups. These results emphasized that silencing of lncRNA UCA1 gene negatively regulates cell growth, differentiation and proliferation.