Related Experiment Video
Updated: Jan 26, 2026
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance
Emre Can Tuysuz1, Sukru Gulluoglu1, Cumhur Kaan Yaltirik2
1Department of Medical Genetics, Yeditepe University Medical School, 34755, Istanbul, Turkey; Department of Genetics and Bioengineering, Yeditepe University, 34755, Istanbul, Turkey.
Abstract:
Chordoma is a rare, slow-growing tumor thought to arise from remnants of embryonic notochord associated with an aggressive outcome. Cancer stem-like cells (CSCs) are related to tumorigenesis, recurrence, and resistance in cancers. Therefore, chordoma CSCs are possible targets for chordoma treatment. In this study, dysregulated miRNAs were determined in chordoma CSCs and identified their role in chordoma. Dysregulated miRNAs were determined via miRNA microarray and validated through qPCR. miRNAs were transiently transfected to the chordoma cell lines and their roles in proliferation, apoptosis, migration and invasion capacities and stem-like properties were identified. Finally, a relationship between clinicopathological features and dysregulated miRNAs has been evaluated among 21 chordoma patients. CD133+CD15+ cells exhibited CSC phenotype with increased CSC- and Epithelial-Mesenchymal Transition (EMT)-related gene expression, invasion, migration, tumorosphere- and colony-forming abilities. In addition, WNT5A, TGF-α, BTG2 and MYCBP genes involved in CSC-related pathways, were targets of miR-140-3p, miR-148a-3p, miR-210-5p and miR-574-5p, respectively. Transfection of CSC-related miRNAs also increased migration and invasion along with stem cell phenotype. Finally, we determined that miR-140-3p and miR-148a-3p expressions correlated with Ki67 while miR-140-3p and TGF-α expressions were correlated with p53. Moreover, MYCBP expression was positively correlated with tumor volume, and metastasis was associated with the expression of miR-210-5p and TGF-α in our patient cohort. Through these findings, we conclude that chordoma CSCs have distinctive miRNA profile, which can regulate stem-like properties of chordoma CSCs.
Insights
Chordoma cancer stem-like cells (CSCs) possess unique microRNA (miRNA) profiles that influence their aggressive behavior and potential for recurrence. Targeting these specific miRNAs could offer new therapeutic strategies for chordoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chordoma is a rare, slow-growing tumor originating from embryonic notochord remnants.
- Cancer stem-like cells (CSCs) are implicated in tumor growth, recurrence, and treatment resistance across various cancers.
- Chordoma CSCs represent a potential therapeutic target for improving patient outcomes.
Purpose of the Study:
- To identify dysregulated microRNAs (miRNAs) in chordoma CSCs.
- To elucidate the functional role of these miRNAs in chordoma progression.
- To explore the correlation between miRNA expression and clinicopathological features in chordoma patients.
Main Methods:
- Chordoma CSCs were isolated and characterized.
- miRNA expression profiling was performed using microarray and validated by qPCR.
- Functional assays (proliferation, apoptosis, migration, invasion) and gene expression analysis were conducted after miRNA transfection.
- Correlation analysis between miRNA expression and clinicopathological data from 21 patients.
Main Results:
- CD133+CD15+ cells displayed CSC characteristics, including enhanced gene expression related to CSCs and Epithelial-Mesenchymal Transition (EMT), invasion, migration, and self-renewal.
- Specific miRNAs (miR-140-3p, miR-148a-3p, miR-210-5p, miR-574-5p) were found to target key genes in CSC-related pathways (WNT5A, TGF-α, BTG2, MYCBP).
- Transfection of these miRNAs modulated CSC properties, migration, and invasion. Expression levels of certain miRNAs and genes correlated with clinical parameters like Ki67, p53, tumor volume, and metastasis.
Conclusions:
- Chordoma CSCs exhibit a distinct miRNA expression profile.
- These miRNAs play a crucial role in regulating the stem-like properties and aggressive behavior of chordoma CSCs.
- The identified miRNA-gene interactions provide potential therapeutic targets for chordoma.
Related Concept Videos
01:18Distinctive Features of Adult Stem Cells vs Cancer Stem Cells
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
01:14Maintenance of the ES Cell State
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
01:33Adult Stem Cells