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NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells

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 chemor...

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Autores principales: Kamdar, Rahul D., Harrington, Brittney S., Attar, Emma, Korrapati, Soumya, Shetty, Jyoti, Zhao, Yongmei, Tran, Bao, Wong, Nathan, House, Carrie D., Annunziata, Christina M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178396/
https://www.ncbi.nlm.nih.gov/pubmed/37175530
http://dx.doi.org/10.3390/ijms24097826
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author Kamdar, Rahul D.
Harrington, Brittney S.
Attar, Emma
Korrapati, Soumya
Shetty, Jyoti
Zhao, Yongmei
Tran, Bao
Wong, Nathan
House, Carrie D.
Annunziata, Christina M.
author_facet Kamdar, Rahul D.
Harrington, Brittney S.
Attar, Emma
Korrapati, Soumya
Shetty, Jyoti
Zhao, Yongmei
Tran, Bao
Wong, Nathan
House, Carrie D.
Annunziata, Christina M.
author_sort Kamdar, Rahul D.
collection PubMed
description 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.
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spelling pubmed-101783962023-05-13 NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells Kamdar, Rahul D. Harrington, Brittney S. Attar, Emma Korrapati, Soumya Shetty, Jyoti Zhao, Yongmei Tran, Bao Wong, Nathan House, Carrie D. Annunziata, Christina M. Int J Mol Sci Article 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. MDPI 2023-04-25 /pmc/articles/PMC10178396/ /pubmed/37175530 http://dx.doi.org/10.3390/ijms24097826 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kamdar, Rahul D.
Harrington, Brittney S.
Attar, Emma
Korrapati, Soumya
Shetty, Jyoti
Zhao, Yongmei
Tran, Bao
Wong, Nathan
House, Carrie D.
Annunziata, Christina M.
NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title_full NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title_fullStr NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title_full_unstemmed NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title_short NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells
title_sort nf-κb signaling modulates mir-452-5p and mir-335-5p expression to functionally decrease epithelial ovarian cancer progression in tumor-initiating cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178396/
https://www.ncbi.nlm.nih.gov/pubmed/37175530
http://dx.doi.org/10.3390/ijms24097826
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