Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance

Tuysuz, Emre Can; Güllüoğlu, Şükrü; Yaltırık, Cumhur Kaan; Ozbey, Utku; Kuşkucu, Ayşegül; Çoban, Esra Aydemir; Şahın, Fikrettin; Türe, Uğur; Bayrak, Ömer Faruk

doi:10.1016/j.yexcr.2019.03.039

Cited by 12 publications

(14 citation statements)

References 69 publications

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“…In those studies, the ALDH activity was used to isolate cancer stem cells, and this activity was correlated with increased tumor initiation capacities and with the expression of genes involved in stem cell maintenance. Cancer stem cells have also been detected in chordoma patients and cell lines (JHC7, U-CH1, and U-CH2) [23][24][25]47]. Here, we confirmed the presence of a subpopulation of cells with a high ALDH activity in 3 different models, but we also correlated this activity with resistance to radiation.…”

Section: Discussionsupporting

confidence: 79%

“…In chordoma, the ALDH activity has been measured in cell lines. These studies demonstrated that a population of U-CH1 cells (between 0.48 and 2.5% depending on the study) have a high ALDH activity [23,24]. In comparison, we found a more important basal rate of ALDH high cells (5% in UT conditions).…”

Section: Discussionsupporting

confidence: 37%

“…This is also the case for bone sarcoma, in which a high ALDH activity is associated with chemotherapy-resistant Ewing sarcoma cells [21]. A population of cells with a high ALDH activity is known to be present in both chordoma patients [22] and cell lines U-CH1 [23], U-CH2, UM-Chor1 [24], and JHC7 [25]. Moreover, the inhibition of ALDH decreases the radioresistance of breast, prostate, and cervical cancer cells [26][27][28].…”

Section: Introductionmentioning

confidence: 83%

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Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

Locquet

Dechaume

Berchard

et al. 2021

Cells

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Chordomas are rare, slow-growing tumors of the axial skeleton. These tumors are locally aggressive and refractory to conventional therapies. Radical surgery and radiation remain the first-line treatments. Despite these aggressive treatments, chordomas often recur and second-line treatment options are limited. The mechanisms underlying chordoma radioresistance remain unknown, although several radioresistant cancer cells have been shown to respond favorably to aldehyde dehydrogenase (ALDH) inhibition. The study of chordoma has been delayed by small patient cohorts and few available models due to the scarcity of these tumors. We thus created cellular 3D models of chordoma by using low-adherence culture systems. Then, we evaluated their radiosensitivity using colony-forming and spheroid size assays. Finally, we determined whether pharmacologically inhibiting ALDH increased their radiosensitivity. We found that 3D cellular models of chordoma (derived from primary, relapse, and metastatic tumors) reproduce the histological and gene expression features of the disease. The metastatic, relapse, and primary spheroids displayed high, medium, and low radioresistance, respectively. Moreover, inhibiting ALDH decreased the radioresistance in all three models.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 37%

Section: Introductionmentioning

confidence: 83%

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Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

Locquet

Dechaume

Berchard

et al. 2021

Cells

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“…Moreover, several miRNAs such as miRNA-140-3p,14 miRNA-1237-3p,15 and miRNA-15516 are identified to be markers correlated with prognosis in chordoma. Besides, altered miRNA profile is also discovered in chordoma cancer stem-like cells (CSCs) which are related to tumorigenesis, recurrence, and resistance in cancers 17. It is well documented that dysregulation of miRNAs affects cancer initiation and progression through altering mRNA expression.…”

Section: Introductionmentioning

confidence: 99%

<p>Upregulation Of miR-149-3p Suppresses Spinal Chordoma Malignancy By Targeting Smad3</p>

Yao¹,

2019

OTT

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PurposeDysregulation of miRNAs plays an important role in the malignancy of different tumors including chordoma. Expression of miR-149-3p was earlier reported to be downregulated in chordoma tissue. However, its biological role remains to be unrevealed in chordoma, especially in spinal chordoma.MethodsExpression of miR-149-3p and Smad3 was detected by RT-qPCR and Western blot. Chordoma malignancy was evaluated by cell proliferation, migration, invasion, and apoptosis using MTT assay, transwell assay, flow cytometry analyzing apoptosis rate, and Western blot-determined expression of Bcl-2, Bax, and cleaved caspase 3, respectively. The target binding between miR-149-3p and Smad3 was predicted by TargetScan Human website and confirmed by luciferase reporter assay and RNA immunoprecipitation. Xenograft tumors were generated, and expression of miR-149-3p and Smad3 was investigated in vivo.ResultsmiR-149-3p was downregulated in spinal chordoma tissues and cells, and its overexpression promoted chordoma cell apoptosis and inhibited proliferation, migration, and invasion in U-CH1 and MUG-Chor1 cells. Unexpectedly, Smad3 was a downstream target of miR-149-3p and negatively correlated with miR-149-3p expression in chordoma tissues. Besides, Smad3 was upregulated in chordoma tissues and its silencing had a similar effect as miR-149-3p overexpression in U-CH1 and MUG-Chor1 cells. Moreover, Smad3 upregulation could partially reverse the tumor-suppressive effect of miR-149-3p in chordoma cells. In vivo, the tumorigenesis of U-CH1 and MUG-Chor1 cells was impaired by upregulated miR-149-3p through decreasing Smad3 expression.ConclusionmiR-149-3p could serve as a tumor suppressor in spinal chordoma through targeting and downregulating Smad3.

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“…MicroRNAs play an important regulatory role in the development of cancer by inhibiting the translation of RNA and the expression of target genes. 4 , 5 Each miRNA can control hundreds of gene targets and participate in multiple gene signaling pathways. 6 Therefore, an miRNA can control a series of biological functions, such as cell proliferation, migration, invasion, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-29b-3p Inhibits the Migration and Invasion of Gastric Cancer Cells by Regulating the Autophagy-Associated Protein MAZ

Zhao¹,

Ye²,

Feng³

et al. 2021

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The purpose of this study was to investigate the relationship between microRNA-29b-3p (miR-29b-3p) and myc-associated zinc finger protein (MAZ) expression and the effects of this interaction on the proliferation, migration, and invasion of gastric cancer cells. Methods: qPCR and Western blots were used to detect the expression of miR-29b-3p and MAZ. The dual luciferase reporter gene system was used to explore whether MAZ is the target of miR-29b-3p. Cell function experiments and a mouse tumorigenesis model were used to determine the effects of miR-29b-3p overexpression and MAZ depletion on proliferation, migration, and invasion in gastric cancer cell lines and on tumor growth.Results: The expression level of miR-29b-3p was low and the expression level of MAZ was high in gastric cancer cells compared with normal human gastric mucosal epithelial cells. MAZ was the target gene of miR-29b-3p. The upregulation of miR-29b-3p reduces the expression of MAZ. Overexpression of miR-29b-3p and downregulation of MAZ inhibited the proliferation and migration of cancer cells and induced apoptosis by controlling the expression of autophagy-related proteins. MiR-29b-3p mimics inhibit tumor growth in mice. Conclusion: MiR-29b-3p inhibits the migration and invasion of gastric cancer cells by regulating the autophagy-related protein MAZ.

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Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance

Cited by 12 publications

References 69 publications

Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

Aldehyde Dehydrogenase, a Therapeutic Target in Chordoma: Analysis in 3D Cellular Models

<p>Upregulation Of miR-149-3p Suppresses Spinal Chordoma Malignancy By Targeting Smad3</p>

MicroRNA-29b-3p Inhibits the Migration and Invasion of Gastric Cancer Cells by Regulating the Autophagy-Associated Protein MAZ

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