Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation

Abstract

MiR-29 family dysregulation occurs in various cancers including breast cancers. We investigated miR-29b-1 functional role in human triple negative breast cancer (TNBC) the most aggressive breast cancer subtype. We found that miR-29b-1-5p was downregulated in human TNBC tissues and cell lines. To assess whether miR-29b-1-5p correlated with TNBC regenerative potential, we evaluated cancer stem cell enrichment in our TNBC cell lines, and found that only MDA-MB-231 and BT-20 produced primary, secondary and tertiary mammospheres, which were progressively enriched in OCT4, NANOG and SOX2 stemness genes. MiR-29b-1-5p expression inversely correlated with mammosphere stemness potential, and miR-29b-1 ectopic overexpression decreased TNBC cell growth, self-renewal, migration, invasiveness and paclitaxel resistance repressing WNT/βcatenin and AKT signaling pathways and stemness regulators. We identified SPINDLIN1 (SPIN1) among predicted miR-29b-1-5p targets. Consistently, SPIN1 was overexpressed in most TNBC tissues and cell lines and negatively correlated with miR-29b-1-5p. Target site inhibition showed that SPIN1 seems to be directly controlled by miR-29b-1-5p. Silencing SPIN1 mirrored the effects triggered by miR-29b-1 overexpression, whereas SPIN1 rescue by SPIN1miScript protector, determined the reversal of the molecular effects produced by the mimic-miR-29b-1-5p. Overall, we show that miR-29b-1 deregulation impacts on multiple oncogenic features of TNBC cells and their renewal potential, acting, at least partly, through SPIN1, and suggest that both these factors should be evaluated as new possible therapeutic targets against TNBC.

Genome-wide mRNA-miRNA profiling uncovers a role of the microRNA miR-29b-1-5p/PHLPP1 signalling pathway inHelicobacter pylori-driven matrix metalloproteinase production in gastric epithelial cells

“…Here, we show that early during infection, HP0175 is associated with augmented expression of miR29b-1-5p. Other independent studies have shown miR-29b-1-5p expression in human triple negative breast cancer cells (Ferrante et al, 2017). miR-29b-1-5p expression is repressed in an hp0175 knockout strain compared with the wild type, and recombinant HP0175 induces miR-29b-1-5p expression.…”

“…It is associated with a higher grade of gastric inflammation (Oghalaie et al, 2016). Other independent studies have shown miR-29b-1-5p expression in human triple negative breast cancer cells (Ferrante et al, 2017). Our earlier studies have shown that depending on the time and/or the dose of infection, HP0175 modulates host cell signalling to trigger either autophagy (Halder et al, 2015) or apoptosis (Basak et al, 2005) in gastric epithelial cells.…”

Driving Integrative Structural Modeling with Serial Capture Affinity Purification

“…The structure of SPIN1 has been solved by X-ray crystallography [31][32][33] . As a result, multiple researchers are pursuing the development of a SPIN1 inhibitor 10,16,[40][41][42][43] . C11orf84, which was recently renamed SPINDOC by Bae and colleagues 9 , is a SPIN1-interacting protein that is less well understood, and the complex containing these two proteins remains poorly characterized.…”

“…We demonstrate the striking capabilities of this technology using a pair of proteins, Spindlin1 (SPIN1) and SPINDOC (c11orf84), which have previously been proposed to directly interact in biochemical 9 and computational 3 studies. SPIN1 is a well characterized histone methylation reader [9][10][11][12][13][14][15][16][17][18][19][20][21] , while SPINDOC has only been defined by its ability to bind SPIN1 9 . In this study, we first characterize the direct interaction and co-diffusion of SPIN1 and SPINDOC in live cells using imaging methods.…”

MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer

“…Of these, the expression of miR-29b-1-5p was significantly upregulated, consistent with our Brca1 Table 3). Interestingly, SPIN1 is among the predicted targets and have been previously identified to be directly targeted by miR-29b-1-5p in breast cancer cell lines 19 .…”