scholarly journals miRNA function and modulation in stem cells and cancer stem cells

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Andrew J. DeCastro ◽  
James DiRenzo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Phenotype ◽  
Pluripotent State ◽  
Differentiated Cells ◽  
Non Coding Rnas ◽  
Multicellular Organisms ◽  
Stem Cell Phenotype

AbstractStem cells belong to a unique class of cells that is collectively responsible for the development and subsequent maintenance of all tissues comprising multicellular organisms. These cells possess unique characteristics that allow them to remain in a pluripotent state, while also continuing to generate differentiated cells. microRNAs, a specialized class of non-coding RNAs, are integral components of the network of pathways that modulates this combination of abilities. This review highlights recent discoveries about the roles miRNAs play in governing stem cell phenotype, and discusses the potential therapeutic utility that miRNAs may have in the treatment of multiple diseases. Additionally, it addresses a novel mode of regulation of stem cell phenotype through lincRNA-mediated modulation of select miRNAs, and the role of secreted, stem cell-derived miRNAs in exerting a paracrine influence on surrounding non-stem cells.

scholarly journals Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory?

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Brescia ◽  
Cristina Richichi ◽  
Giuliana Pelicci
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Cell Phenotype ◽  
Multiple Tumor ◽  
Early Results ◽  
Tumorigenic Potential ◽  
Tumor Types

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge.

scholarly journals The Role of Nerve Growth Factor in Maintaining Proliferative Capacity, Colony-Forming Efficiency, and the Limbal Stem Cell Phenotype

Stem Cells ◽  
2018 ◽  
Vol 37 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Sai Kolli ◽  
Sanja Bojic ◽  
Ali E. Ghareeb ◽  
Marzena Kurzawa-Akanbi ◽  
Francisco C. Figueiredo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Phenotype ◽  
Proliferative Capacity ◽  
Colony Forming Efficiency ◽  
Forming Efficiency ◽  
Limbal Stem Cell ◽  
Stem Cell Phenotype

scholarly journals PPARγ2 Regulates a Molecular Signature of Marrow Mesenchymal Stem Cells

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-13 ◽  
Author(s):  
K. R. Shockley ◽  
C. J. Rosen ◽  
G. A. Churchill ◽  
B. Lecka-Czernik
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Molecular Signature ◽  
Cell Phenotype ◽  
Differentiation Potential ◽  
Gene Markers ◽  
Therapeutic Consequences ◽  
Expression Of Genes ◽  
Stem Cell Phenotype

Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms. Bone marrow mesenchymal stromal/stem cells (MSC) contain a compartment that provides progeny with bone forming osteoblasts and fat laden adipocytes as well as fibroblasts, chondrocytes, and muscle cells. In addition, marrow MSC provide an environment for support of hematopoiesis, including the development of bone resorbing osteoclasts. The PPARγ2 nuclear receptor is an adipocyte-specific transcription factor that controls marrow MSC lineage allocation toward adipocytes and osteoblasts. Increased expression of PPARγ2 with aging correlates with changes in the MSC status in respect to both their intrinsic differentiation potential and production of signaling molecules that contribute to the formation of a specific marrow microenvironment. Here, we investigated the effect of PPARγ2 on MSC molecular signature in respect to the expression of gene markers associated exclusively with stem cell phenotype, as well as genes involved in the formation of a stem cell supporting marrow environment. We found that PPARγ2 is a powerful modulator of stem cell-related gene expression. In general, PPARγ2 affects the expression of genes specific for the maintenance of stem cell phenotype, including LIF, LIF receptor, Kit ligand, SDF-1, Rex-1/Zfp42, and Oct-4. Moreover, the antidiabetic PPARγagonist TZD rosiglitazone specifically affects the expression of “stemness” genes, including ABCG2, Egfr, and CD44. Our data indicate that aging and antidiabetic TZD therapy may affect mesenchymal stem cell phenotype through modulation of PPARγ2 activity. These observations may have important therapeutic consequences and indicate a need for more detailed studies of PPARγ2 role in stem cell biology.

scholarly journals HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

2015 ◽  
Vol 112 (45) ◽  
pp. E6215-E6223 ◽  
Author(s):  
Huimin Zhang ◽  
Haiquan Lu ◽  
Lisha Xiang ◽  
John W. Bullen ◽  
Chuanzhao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Cell Phenotype

Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription of the CD47 gene in hypoxic breast cancer cells. Knockdown of HIF activity or CD47 expression increased the phagocytosis of breast cancer cells by bone marrow-derived macrophages. CD47 expression was increased in mammosphere cultures, which are enriched for cancer stem cells, and CD47 deficiency led to cancer stem cell depletion. Analysis of datasets derived from thousands of patients with breast cancer revealed that CD47 expression was correlated with HIF target gene expression and with patient mortality. Thus, CD47 expression contributes to the lethal breast cancer phenotype that is mediated by HIF-1.

scholarly journals Glioblastoma Stem Cells as a New Therapeutic Target for Glioblastoma

2015 ◽  
Vol 9 ◽  
pp. CMO.S30271 ◽  
Author(s):  
Rasime Kalkan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Fatal Outcome ◽  
Cellular Heterogeneity ◽  
Cell Phenotype ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Stem Cell

Primary and secondary glioblastomas (GBMs) are two distinct diseases. The genetic and epigenetic background of these tumors is highly variable. The treatment procedure for these tumors is often unsuccessful because of the cellular heterogeneity and intrinsic ability of the tumor cells to invade healthy tissues. The fatal outcome of these tumors promotes researchers to find out new markers associated with the prognosis and treatment planning. In this communication, the role of glioblastoma stem cells in tumor progression and the malignant behavior of GBMs are summarized with attention to the signaling pathways and molecular regulators that are involved in maintaining the glioblastoma stem cell phenotype. A better understanding of these stem cell-like cells is necessary for designing new effective treatments and developing novel molecular strategies to target glioblastoma stem cells. We discuss hypoxia as a new therapeutic target for GBM. We focus on the inhibition of signaling pathways, which are associated with the hypoxia-mediated maintenance of glioblastoma stem cells, and the knockdown of hypoxia-inducible factors, which could be identified as attractive molecular target approaches for GBM therapeutics.

scholarly journals The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype

Cell Cycle ◽  
2009 ◽  
Vol 8 (20) ◽  
pp. 3274-3284 ◽  
Author(s):  
John M. Heddleston ◽  
Zhizhong Li ◽  
Roger E. McLendon ◽  
Anita B. Hjelmeland ◽  
Jeremy N. Rich
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Phenotype ◽  
Glioblastoma Stem Cells ◽  
Cancer Stem Cell Phenotype ◽  
Stem Cell Phenotype

scholarly journals LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. Results ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. Conclusions YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals A Systematic Review to Clarify the Prognostic Values of CD44 and CD44+CD24- Phenotype in Triple-Negative Breast Cancer Patients: Lessons Learned and The Road Ahead

2021 ◽  
Vol 11 ◽  
Author(s):  
Mahdi Abdoli Shadbad ◽  
Negar Hosseinkhani ◽  
Zahra Asadzadeh ◽  
Afshin Derakhshani ◽  
Noora Karim Ahangar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Phenotype ◽  
Stem Cell Markers ◽  
Advanced Tumor Stage

As a unique population of tumor bulk, cancer stem cells have been implicated in tumor relapse and chemoresistance in triple-negative breast cancer (TNBC). Therefore, understanding the phenotype of cancer stem cells can pave the way for introducing novel molecular targeted therapies for treating TNBC patients. Preclinical studies have identified CD44+CD24-/low as a cancer stem cell phenotype; however, clinical studies have reported seemingly controversial results regarding the prognostic values of CD44 and CD44+CD24-/low phenotype in TNBC patients. To critically review the clinicopathological significance and prognostic values of CD44 and CD44+CD24-/low phenotype in TNBC patients, the Scopus, Embase, PubMed, and Web of Science databases were systematically searched to obtain the relevant records published before 20 October 2020. Based on nine included studies, CD44 and CD44+CD24-/low phenotype are associated with inferior prognosis in TNBC patients. Moreover, these cancer stem cell markers have been associated with advanced tumor stage, tumor size, higher tumor grade, tumor metastasis, and lymphatic involvement in TNBC patients. Our evidence has also indicated that, unlike the treatment-naïve TNBC patients, the tumoral cells of chemoradiotherapy-treated TNBC patients can upregulate the CD44+CD24-/low phenotype and establish an inverse association with androgen receptor (AR), leading to the inferior prognosis of affected patients. In summary, CD44 and CD44+CD24-/low phenotype can be utilized to determine TNBC patients’ prognosis in the pathology department as a routine practice, and targeting these phenotypes can substantially improve the prognosis of TNBC patients.

scholarly journals iNOS promotes CD24+CD133+liver cancer stem cell phenotype through a TACE/ADAM17-dependent Notch signaling pathway

2018 ◽  
Vol 115 (43) ◽  
pp. E10127-E10136 ◽  
Author(s):  
Ronghua Wang ◽  
Yawen Li ◽  
Allan Tsung ◽  
Hai Huang ◽  
Qiang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Notch Signaling ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Cell Phenotype ◽  
Stem Cell Markers ◽  
Notch1 Signaling

The inducible nitric oxide synthase (iNOS) is associated with more aggressive solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer stem cells promotes cancer progression and requires Notch cleavage by ADAM (a disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem cell markers CD24 and CD133 in the tumors of patients with HCC was associated with greater iNOS expression and worse outcomes. The expression of iNOS in CD24+CD133+LCSCs, but not CD24−CD133−LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as well as accelerating HCC initiation and tumor formation in the mouse xenograft tumor model. iNOS/NO led to Notch1 signaling through a pathway involving the soluble guanylyl cyclase/cGMP/PKG-dependent activation of TACE/ADAM17 and up-regulation of iRhom2 in LCSCs. In patients with HCC, higher TACE/ADAM17 expression and Notch1 activation correlated with poor prognosis. These findings link iNOS to Notch1 signaling in CD24+CD133+LCSCs through the activation of TACE/ADAM17 and identify a mechanism for how iNOS contributes to progression of CD24+CD133+HCC.

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