NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells.
Rahul D KamdarBrittney S HarringtonEmma AttarSoumya KorrapatiJyoti ShettyYongmei ZhaoBao TranNathan WongCarrie D HouseChristina M AnnunziataPublished in: International journal of molecular sciences (2023)
Epithelial ovarian cancer (EOC) remains the fifth leading cause of cancer-related death in women worldwide, partly due to the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that promote disease relapse. We previously described a role for the NF-κB pathway in promoting TIC chemoresistance and survival through NF-κB transcription factors (TFs) RelA and RelB, which regulate genes important for the inflammatory response and those associated with cancer, including microRNAs (miRNAs). We hypothesized that NF-κB signaling differentially regulates miRNA expression through RelA and RelB to support TIC persistence. Inducible shRNA was stably expressed in OV90 cells to knockdown RELA or RELB ; miR-seq analyses identified differentially expressed miRNAs hsa-miR-452-5p and hsa-miR-335-5p in cells grown in TIC versus adherent conditions. We validated the miR-seq findings via qPCR in TIC or adherent conditions with RELA or RELB knocked-down. We confirmed decreased expression of hsa-miR-452-5p when either RELA or RELB were depleted and increased expression of hsa-miR-335-5p when RELA was depleted. Either inhibiting miR-452-5p or mimicking miR-335-5p functionally decreased the stem-like potential of the TICs. These results highlight a novel role of NF-κB TFs in modulating miRNA expression in EOC cells, thus opening a better understanding toward preventing recurrence of EOC.
Keyphrases
- induced apoptosis
- signaling pathway
- cell cycle arrest
- poor prognosis
- pi k akt
- lps induced
- long non coding rna
- oxidative stress
- obsessive compulsive disorder
- cell death
- cell proliferation
- nuclear factor
- single cell
- squamous cell carcinoma
- metabolic syndrome
- immune response
- binding protein
- toll like receptor
- pregnant women
- free survival
- lipopolysaccharide induced
- dna binding