The human PMR1 endonuclease stimulates cell motility by down regulating miR-200 family microRNAs

Gu, Shan Qing; Gallego‐Perez, Daniel; McClory, Sean P.; Shi, Junfeng; Han, Joonhee; Lee, L. James; Schoenberg, Daniel R.

doi:10.1093/nar/gkw497

Cited by 10 publications

(10 citation statements)

References 38 publications

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“…These cells were plated on microtextured polydimethylsiloxane (PDMS) surfaces ( Fig. 1B), which were fabricated via replica molding from photolithographically fabricated silicon masters, and were designed as an array of parallel ridges and grooves with dimensions that have been previously tested in cancer cell dissemination studies (~2 µm × 2 µm with 2 µm spacing) [10][11][12][13] . MDSC motility was monitored at the single-clone level in real time via time-lapse microscopy.…”

Section: Resultsmentioning

confidence: 99%

“…www.nature.com/scientificreports www.nature.com/scientificreports/ conclusions Micro-and nanoscale technologies have been used extensively to probe and/or modulate various aspects of cell biology for medical applications [10][11][12][13][14][15][26][27][28][29][30][31][32][33][34][35][36] , especially in cancer therapy and diagnostics 3,37-42 . Here we used microscale engineering tools to demonstrate that tumor-associated MDSCs exhibit structurally guided migration patterns, similar to invasive cancerous cells.…”

Section: Mdsc Subpopulations Exhibit Different Dissemination Capabilimentioning

confidence: 99%

“…While targeting the dissemination-based mechanisms by which MDSCs infiltrate the tumor niche could be a viable alternative strategy against MDSC-driven immunosuppression at the tumor site, our understanding of such mechanisms for MDSCs is limited compared to what we know about the dissemination modalities of cancerous tumor cells. Structurally guided migration has been known to play a key role in the escape of cancerous cells from the primary tumor, as well as in dissemination and metastasis [10][11][12][13][14][15] . Nevertheless, to the best of our knowledge, no study has probed MDSC motility under structurally guided dissemination conditions.…”

mentioning

confidence: 99%

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Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations

Duarte‐Sanmiguel

Shukla

Benner

et al. 2020

Sci Rep

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Myeloid-derived suppressor cells (MDScs) are immune cells that exert immunosuppression within the tumor, protecting cancer cells from the host's immune system and/or exogenous immunotherapies.While current research has been mostly focused in countering MDSC-driven immunosuppression, little is known about the mechanisms by which MDSCs disseminate/infiltrate cancerous tissue. This study looks into the use of microtextured surfaces, coupled with in vitro and in vivo cellular and molecular analysis tools, to videoscopically evaluate the dissemination patterns of MDSCs under structurally guided migration, at the single-cell level. MDSCs exhibited topographically driven migration, showing significant intra-and inter-population differences in motility, with velocities reaching ~40 μm h −1 . Downstream analyses coupled with single-cell migration uncovered the presence of specific MDSC subpopulations with different degrees of tumor-infiltrating and anti-inflammatory capabilities. Granulocytic MDSCs showed a ~≥3-fold increase in maximum dissemination velocities and traveled distances, and a ~10-fold difference in the expression of pro-and anti-inflammatory markers. Prolonged culture also revealed that purified subpopulations of MDSCs exhibit remarkable plasticity, with homogeneous/sorted subpopulations giving rise to heterogenous cultures that represented the entire hierarchy of MDSC phenotypes within 7 days. These studies point towards the granulocytic subtype as a potential cellular target of interest given their superior dissemination ability and enhanced antiinflammatory activity.The tumor microenvironment is highly heterogeneous in nature, with cancerous cells co-habiting with both stromal and immune cells. Such complex cellular interplay plays a central role in modulating tumor progression. Myeloid-derived suppressor cells (MDSCs), in particular, have been known to exert immunosuppressive activity in the tumor niche, which protects cancerous cells from the host immune system and/or different therapeutic modalities 1,2 . While a lot of research has been devoted to developing advanced drugs and drug delivery systems to target cancerous cells 3-5 , and/or blocking MDSC-driven immunosuppression within the tumor niche 6,7 , less is known about the motility mechanisms by which MDSCs disseminate and colonize the tumor in the first place.MDSCs are innate immune cells that are highly expanded in cancer patients 2 . These cells tend to infiltrate tumors and lymphoid tissues, and their levels correlate with increased tumor burden and limited survival in a variety of malignancies 6-9 . MDSCs specifically contribute to the loss of immune effector cell function and reduce the efficacy of immunotherapies. As such, MDSCs have emerged as an attractive therapeutic target in

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Section: Resultsmentioning

confidence: 99%

Section: Mdsc Subpopulations Exhibit Different Dissemination Capabilimentioning

confidence: 99%

mentioning

confidence: 99%

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Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations

Duarte‐Sanmiguel

Shukla

Benner

et al. 2020

Sci Rep

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“…The cell migration velocity of HFBSCs was relatively fast (80.5 ± 6.1 μm/h) as compared to other cell types as determined in wound-healing migration assays [ 20 – 23 ], indicating that they conserved the migratory nature of NCSCs. Migration of cells is to a large extent dependent on the type of extracellular matrix (ECM) and the presence of chemical attractants, such as growth factors.…”

Section: Discussionmentioning

confidence: 99%

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

et al. 2017

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Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair.

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“…PMR1 exhibits the properties of a proto-oncogene and is an effector of the EFGR (epidermal growth factor receptor) signalling pathway. Recently obtained data shows that increased migration activity and invasiveness of MCF-7 breast cancer cells is associated with high PMR1 activity, the targets of which are miRNAs of the miR-200 family, which are responsible for controlling adhesion and invasion (Bracken et al, 2014; Gu et al, 2016; Perdigão-Henriques et al, 2016; Figure 1F ).…”

Section: The Role Of Endogenous Mammalian Rnases In the Control Of Inmentioning

confidence: 97%

Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases

Миронова

Vlassov

2019

Front. Pharmacol.

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Tumour progression is accompanied by rapid cell proliferation, loss of differentiation, the reprogramming of energy metabolism, loss of adhesion, escape of immune surveillance, induction of angiogenesis, and metastasis. Both coding and regulatory RNAs expressed by tumour cells and circulating in the blood are involved in all stages of tumour progression. Among the important tumour-associated RNAs are intracellular coding RNAs that determine the routes of metabolic pathways, cell cycle control, angiogenesis, adhesion, apoptosis and pathways responsible for transformation, and intracellular and extracellular non-coding RNAs involved in regulation of the expression of their proto-oncogenic and oncosuppressing mRNAs. Considering the diversity/variability of biological functions of RNAs, it becomes evident that extracellular RNAs represent important regulators of cell-to-cell communication and intracellular cascades that maintain cell proliferation and differentiation. In connection with the elucidation of such an important role for RNA, a surge in interest in RNA-degrading enzymes has increased. Natural ribonucleases (RNases) participate in various cellular processes including miRNA biogenesis, RNA decay and degradation that has determined their principal role in the sustention of RNA homeostasis in cells. Findings were obtained on the contribution of some endogenous ribonucleases in the maintenance of normal cell RNA homeostasis, which thus prevents cell transformation. These findings directed attention to exogenous ribonucleases as tools to compensate for the malfunction of endogenous ones. Recently a number of proteins with ribonuclease activity were discovered whose intracellular function remains unknown. Thus, the comprehensive investigation of physiological roles of RNases is still required. In this review we focused on the control mechanisms of cell transformation by endogenous ribonucleases, and the possibility of replacing malfunctioning enzymes with exogenous ones.

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The human PMR1 endonuclease stimulates cell motility by down regulating miR-200 family microRNAs

Cited by 10 publications

References 38 publications

Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations

Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Surveillance of Tumour Development: The Relationship Between Tumour-Associated RNAs and Ribonucleases

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