A MicroRNA/Ubiquitin Ligase Feedback Loop Regulates Slug-Mediated Invasion in Breast Cancer

Neoplasia : an International Journal for Oncology Research
Rajesh Kumar ManneManas Kumar Santra

Abstract

The transformation of a normal cell to cancer requires the derail of multiple pathways. Normal signaling in a cell is regulated at multiple stages by the presence of feedback loops, calibration of levels of proteins by their regulated turnover, and posttranscriptional regulation, to name a few. The tumor suppressor protein FBXO31 is a component of the SCF E3 ubiquitin ligase and is required to arrest cells at G1 following genotoxic stresses. Due to its growth-suppression activity, it is underexpressed in many cancers. However, the molecular mechanism underlying the translational regulation of FBXO31 remains unclear. Here we show that the oncogenic microRNAs miR-93 and miR-106a repress FBXO31, resulting in the upregulation of Slug, which is involved in epithelial-mesenchymal transition and cell invasion. FBXO31 targets and ubiquitylates Slug for proteasomal degradation. However, this mechanism is repressed in breast tumors where miR-93 and miR-106a are overexpressed. Our study further unravels an interesting mechanism whereby Slug drives the expression of miR-93 and miR-106a, thus establishing a positive feedback loop to maintain an invasive phenotype. Together, these results establish the presence of interplay between microRNAs...Continue Reading

Citations

Feb 5, 2019·The Journal of Pathology·Debasish PaulManas Kumar Santra
Mar 21, 2018·Oncology Letters·Yuyong TanJirong Huo
Aug 8, 2020·Frontiers in Molecular Biosciences·Esta SterneckKuppusamy Balamurugan
Mar 3, 2019·Journal of Experimental & Clinical Cancer Research : CR·Bo-Wen LiuXu-Chen Cao
Jul 17, 2020·Non-coding RNA·Jun Sheng Wong, Yoke Kqueen Cheah
Sep 24, 2019·Cancer Letters·Min LinZhi-Wei Wang

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Methods Mentioned

BETA
transfection
Assay
PCR
electrophoresis
Immunoprecipitation
Ubiquitination
co-immunoprecipitation
ChIP

Software Mentioned

Sigma Stat
ImageJ
Tscratch
Clustal Omega

Related Concepts