NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells.
NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells.
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NF-κB信号调节miR-452-5p和miR-335-5p的表达，在功能性上减少肿瘤起始细胞中卵巢上皮癌的进展。
DOI：
10.3390/ijms24097826
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发表时间：
2023-04-25
影响因子：
5.6
通讯作者：
Annunziata, Christina M.
中科院分区：
文献类型：
--
作者：
Kamdar, Rahul D.;Harrington, Brittney S.;Attar, Emma;Korrapati, Soumya;Shetty, Jyoti;Zhao, Yongmei;Tran, Bao;Wong, Nathan;House, Carrie D.;Annunziata, Christina M.
上皮性卵巢癌(EOC)仍然是全球女性癌症相关死亡的第五大原因，部分原因是化疗耐药的干细胞样肿瘤启动细胞(TICs)的存活促进了疾病的复发。我们先前描述了NF-κB途径通过核因子-κB转录因子(TF)RelA和RelB在促进肿瘤耐药和生存中的作用，这两个转录因子调控着对炎症反应和与癌症相关的重要基因，包括microRNAs(MiRNAs)。我们假设，NF-miRNAB信号通过RelA和RelB差异地调节κ的表达，以支持TIC持续性。可诱导的shRNA在OV90细胞中稳定表达，抑制RERA或RELB；miR-seq分析发现，在TIC和贴壁条件下生长的细胞中存在差异表达的miRNAs hsa-miR-452-5p和hsa-miR-335-5p。我们通过定量聚合酶链式反应来验证miR-seq的发现，在TIC中或在RELA或RELB被敲除的粘连条件下。我们证实，当RELA或RELB耗尽时，hsa-miR-452-5p的表达减少，而当relA耗尽时，hsa-miR-335-5p的表达增加。抑制miR-452-5P或模仿miR-335-5P功能上均可降低抽搐的茎样电位。这些结果突显了NF-κB转录因子在调控卵巢癌细胞miRNA表达中的新作用，从而为预防卵巢癌的复发提供了更好的理解。
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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DOI：
10.18632/aging.202657
发表时间：
2021-03-03
期刊：
Aging
影响因子：
--
作者：
Lin X;Han L;Gu C;Lai Y;Lai Q;Li Q;He C;Meng Y;Pan L;Liu S;Li A
通讯作者：
Li A
影响因子：
4
作者：
Liu R;Guo H;Lu S
通讯作者：
Lu S
影响因子：
11.2
作者：
House CD;Jordan E;Hernandez L;Ozaki M;James JM;Kim M;Kruhlak MJ;Batchelor E;Elloumi F;Cam MC;Annunziata CM
通讯作者：
Annunziata CM
影响因子：
12.3
作者：
Liu, Weijun;Wang, Xiaowei
通讯作者：
Wang, Xiaowei
影响因子：
5.4
作者：
Li, Yanhong;Yao, Li;Zhang, Wei
通讯作者：
Zhang, Wei