Unknown

Dataset Information

0

MiR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth.


ABSTRACT: Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-?B activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma.

SUBMITTER: Fulciniti M 

PROVIDER: S-EPMC4742623 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications


Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function  ...[more]

Similar Datasets

| S-EPMC4047128 | biostudies-literature
| S-EPMC3868926 | biostudies-literature
| S-EPMC1838740 | biostudies-literature
| S-EPMC9265408 | biostudies-literature
2022-02-16 | PXD023455 | Pride
| S-EPMC2867902 | biostudies-other
| S-EPMC4047387 | biostudies-literature
| S-EPMC218699 | biostudies-literature
| S-EPMC6115388 | biostudies-literature
| S-EPMC3424044 | biostudies-literature