Matrix metalloprotease 16 expression is downregulated by microRNA-146a in spontaneously differentiating Caco-2 cells

2012-02-01
Cellular differentiation in the gut is vital in maintaining the cellular and functional specialization of the epithelial layer. MicroRNAs (miRNAs) have recently emerged as one of the key players in orchestrating the differentiation process in the gut. Using the spontaneously differentiating Caco-2 cell line, we observed an increased expression of miR-146a but not miR-146b in the course of differentiation. Bioinformatic analyses revealed that the membrane type matrix metalloprotease 16 (MMP16, MT3-MMP) was a predicted target of miR-146a and a decrease in the mRNA and protein expression of MMP16 was observed in the course of differentiation. Transfection of a luciferase reporter vector containing the 3'UTR of MMP16 showed decreased luciferase activity due to miR-146a expression. With forced expression of miR-146a in undifferentiated Caco-2 cells, a decrease in the mRNA and protein levels of MMP16 and a lower gelatinase activity in a gelatin zymogram were observed. Additionally, forced expression of miR-146a in HT-29 colon cancer cells also resulted in decreased expression of MMP16, along with a decrease in the invasion through Matrigel. Taken together, we have shown here that MMP16 is regulated by miR-146a in spontaneously differentiated Caco-2 cells. As MMP16 activates the zymogen of MMP2, which is known to degrade extracellular matrix proteins, the regulation of MMP16 by miR-146a may account, at least in part, for lower motility of well-differentiated cells.
DEVELOPMENT GROWTH & DIFFERENTIATION

Suggestions

Protein-Protein Interactions in Live Cells: Reinventing the Wheel
Son, Çağdaş Devrim (2018-12-13)
G protein-coupled receptors (GPCRs) are membrane proteins that mediate physiologicalresponse to a diverse array of stimuli. In humans, they mediate the action of hundreds ofpeptide hormones, sensory stimuli, odorants, neurotransmitters, and chemokines. GPCRs alsoare targets for ~40% of all currently marketed pharmaceuticals. These receptors traditionallybeen thought to act as monomeric units. However, recent evidence suggests that GPCRs mayform dimers as part of their normal trafficking and function. While ...
Transcriptional regulatory proteins in central carbon metabolism ofPichia pastorisandSaccharomyces cerevisiae
Kalender, Ozge; Çalık, Pınar (2020-09-01)
System-wide interactions in living cells and discovery of the diverse roles of transcriptional regulatory proteins that are mediator proteins with catalytic domains and regulatory subunits and transcription factors in the cellular pathways have become crucial for understanding the cellular response to environmental conditions. This review provides information for future metabolic engineering strategies through analyses on the highly interconnected regulatory networks inSaccharomyces cerevisiaeandPichia past...
Optimization of internal tagging of inhibitory G-proteins for investigating their interactions with dopamine receptor D2 via fret method
Özcan, Gizem; Son, Çağdaş Devrim; Özçubukçu, Salih; Department of Biochemistry (2016)
G-Protein Coupled Receptors (GPCRs) constitute a large family of receptors which act by sensing the molecules outside the cell and start a signal transduction inside the cell through interacting with their associated G-proteins. This interaction results in activation or repression of related signaling pathways via associated secondary messengers. Dopamine receptor D2 (D2R) is a member of D2-like Dopamine Receptor group, which also belongs to the GPCR family. It is known that D2R has critical roles in emotio...
Enhanced expression of HNF4 alpha during intestinal epithelial differentiation is involved in the activation of ER stress
Tuncer, Sinem; Sade-Memişoğlu, Aslı; Keşküş, Ayşe Gökçe; Sheraj, Ilir; Güner, Güneş; Akyol, Aytekin; Banerjee, Sreeparna (WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019-12)
Intestinal epithelial cells are derived from stem cells at the crypts that undergo differentiation into transit-amplifying cells, which in turn form terminally differentiated enterocytes as these cells reach the villus. Extensive alterations in both transcriptional and translational programs occur during differentiation, which can induce the activation of cellular stress responses such as ER stress-related unfolded protein response (UPR) and autophagy, particularly in the cells that are already committed to...
DynaDom: structure-based prediction of T cell receptor inter-domain and T cell receptor-peptide-MHC (class I) association angles
Hoffmann, Thomas; Marıon, Antoıne; Antes, Iris (Springer Science and Business Media LLC, 2017-02-02)
Background: T cell receptor (TCR) molecules are involved in the adaptive immune response as they distinguish between self- and foreign-peptides, presented in major histocompatibility complex molecules (pMHC). Former studies showed that the association angles of the TCR variable domains (Va/V beta) can differ significantly and change upon binding to the pMHC complex. These changes can be described as a rotation of the domains around a general Center of Rotation, characterized by the interaction of two highly...
Citation Formats
E. ASTARCI, A. E. Erson Bensan, and S. Banerjee, “Matrix metalloprotease 16 expression is downregulated by microRNA-146a in spontaneously differentiating Caco-2 cells,” DEVELOPMENT GROWTH & DIFFERENTIATION, pp. 216–226, 2012, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/45777.