Unknown

Dataset Information

0

MicroRNA-30c-2-3p negatively regulates NF-?B signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer.


ABSTRACT: Nuclear Factor kappa B (NF-?B) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER-) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF-?B regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post-transcriptional level. In a previous genome-wide miRNA screen, we had identified miR-30c-2-3p as one of the strongest negative regulators of NF-?B signaling. Here we have uncovered the underlying molecular mechanisms and its consequences in breast cancer. In vitro results show that miR-30c-2-3p directly targets both TNFRSF1A-associated via death domain (TRADD), an adaptor protein of the TNFR/NF-?B signaling pathway, and the cell cycle protein Cyclin E1 (CCNE1). Ectopic expression of miR-30c-2-3p downregulated essential cytokines IL8, IL6, CXCL1, and reduced cell proliferation as well as invasion in MDA-MB-231 breast cancer cells. RNA interference (RNAi) induced silencing of TRADD phenocopied the effects on invasion and cytokine expression caused by miR-30c-2-3p, while inhibition of CCNE1 phenocopied the effects on cell proliferation. We further confirmed the tumor suppressive role of this miRNA using a dataset of 781 breast tumors, where higher expression was associated with better survival in breast cancer patients. In summary we have elucidated the mechanism by which miR-30c-2-3p negatively regulates NF-?B signaling and cell cycle progression in breast cancer.

SUBMITTER: Shukla K 

PROVIDER: S-EPMC5528752 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer.

Shukla Kirti K   Sharma Ashwini Kumar AK   Ward Aoife A   Will Rainer R   Hielscher Thomas T   Balwierz Aleksandra A   Breunig Christian C   Münstermann Ewald E   König Rainer R   Keklikoglou Ioanna I   Wiemann Stefan S  

Molecular oncology 20150210 6


Nuclear Factor kappa B (NF-κB) signaling is frequently deregulated in a variety of cancers and is constitutively active in estrogen receptor negative (ER-) breast cancer subtypes. These molecular subtypes of breast cancer are associated with poor overall survival. We focused on mechanisms of NF-κB regulation by microRNAs (miRNAs), which regulate eukaryotic gene expression at the post-transcriptional level. In a previous genome-wide miRNA screen, we had identified miR-30c-2-3p as one of the stron  ...[more]

Similar Datasets

| S-EPMC7066027 | biostudies-literature
| S-EPMC7004518 | biostudies-literature
| S-EPMC5072442 | biostudies-literature
| S-EPMC8788908 | biostudies-literature
| S-EPMC2763324 | biostudies-literature
| S-EPMC4627347 | biostudies-literature
| S-EPMC4922628 | biostudies-literature
| S-EPMC5494817 | biostudies-other
| S-EPMC8658496 | biostudies-literature
| S-EPMC7398873 | biostudies-literature