scholarly journals LINC00115 promotes stemness and inhibits apoptosis of ovarian cancer stem cells by upregulating SOX9 and inhibiting the Wnt/β-catenin pathway through competitively binding to microRNA-30a

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Hou ◽  
Luo Jiang
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Dna Damage ◽  
Caspase 3 ◽  
Gene Expression Omnibus ◽  
Ovarian Cancer Stem Cells ◽  
Non Coding Rnas ◽  
Microarray Datasets ◽  
Cell Supernatant

Abstract Objective Long non-coding RNAs (lncRNAs) and microRNAs (miRs) are differentially expressed in ovarian cancer (OC) cells and influence OC progression. This study intended to explore the underlying roles of LINC00115 and miR-30a in OC. Methods Gene Expression Omnibus database was used to find OC microarray datasets and bioinformatics analysis predicted the potential molecular mechanism of OC. OC stem cells (OCSCs) surface marker was isolated from human OC cell line and identified. CD133+ OCSCs were transfected with LINC00115, miR-30a and SOX9 alone or together to detect sphere-forming ability and apoptosis of OCSCs. Caspase-3 activity and DNA damage in cell supernatant were detected. The levels of CD44, NANOG, POU5F1, LINC00115, CD133, miR-30a and SOX9 were measured. Then sh-LNC00115-treated OCSCs were added with Wnt/β-catenin activator SKL2001 to observe the changes of cell stemness and activity. Finally, animal models were established to evaluate the effect of LINC00115 on OCSC in vivo. Results LINC00115 and SOX9 were highly expressed in OC, while miR-30a was lowly expressed. After silencing LINC00115 or overexpressing miR-30a, the sphere-forming rate of CD133+ OCSC and levels of CD133, CD44, NANOG and POU5F1 decreased, while apoptotic rate, Caspase-3 activity and histone-related DNA damage increased. SOX9 reversed these trends. Additionally, LINC00115 could bind to miR-30a and miR-30a could target SOX9. SKL2001 partially reversed cell stemness and activity in sh-LNC00115-treated OCSCs. Finally, silencing LINC00115 could inhibit OCSCs growth in vivo. Conclusion LINC00115 promoted stemness and inhibited apoptosis of OCSCs by upregulating SOX9 and in activating the Wnt/β-catenin pathway through competitively binding to miR-30a.

scholarly journals TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo

2016 ◽  
Vol 15 (6) ◽  
pp. 1279-1290 ◽  
Author(s):  
Ayesha B. Alvero ◽  
Andrew Heaton ◽  
Eydis Lima ◽  
Mary Pitruzzello ◽  
Natalia Sumi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ovarian Cancer Stem Cells

scholarly journals Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells

2015 ◽  
Vol 112 (14) ◽  
pp. 4411-4416 ◽  
Author(s):  
Amit Kumar Srivastava ◽  
Chunhua Han ◽  
Ran Zhao ◽  
Tiantian Cui ◽  
Yuntao Dai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Dna Polymerase ◽  
Ovarian Cancer Stem Cells ◽  
Primary Tumors ◽  
Tumor Relapse ◽  
Induced Apoptosis

Cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance are believed to be responsible for treatment failure and tumor relapse in ovarian cancer patients. However, it is still unclear how CSCs survive DNA-damaging agent treatment. Here, we report an elevated expression of DNA polymerase η (Pol η) in ovarian CSCs isolated from both ovarian cancer cell lines and primary tumors, indicating that CSCs may have intrinsically enhanced translesion DNA synthesis (TLS). Down-regulation of Pol η blocked cisplatin-induced CSC enrichment both in vitro and in vivo through the enhancement of cisplatin-induced apoptosis in CSCs, indicating that Pol η-mediated TLS contributes to the survival of CSCs upon cisplatin treatment. Furthermore, our data demonstrated a depletion of miR-93 in ovarian CSCs. Enforced expression of miR-93 in ovarian CSCs reduced Pol η expression and increased their sensitivity to cisplatin. Taken together, our data suggest that ovarian CSCs have intrinsically enhanced Pol η-mediated TLS, allowing CSCs to survive cisplatin treatment, leading to tumor relapse. Targeting Pol η, probably through enhancement of miR-93 expression, might be exploited as a strategy to increase the efficacy of cisplatin treatment.

scholarly journals The Metabolic Inhibitor CPI-613 Negates Treatment Enrichment of Ovarian Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1678 ◽  
Author(s):  
Chiara Bellio ◽  
Celeste DiGloria ◽  
David R. Spriggs ◽  
Rosemary Foster ◽  
Whitfield B. Growdon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Tca Cycle ◽  
Metabolic Inhibitor ◽  
Ovarian Cancer Stem Cells ◽  
Platinum Resistant

One of the most significant therapeutic challenges in the treatment of ovarian cancer is the development of recurrent platinum-resistant disease. Cancer stem cells (CSCs) are postulated to contribute to recurrent and platinum-resistant ovarian cancer (OvCa). Drugs that selectively target CSCs may augment the standard of care cytotoxics and have the potential to prevent and/or delay recurrence. Increased reliance on metabolic pathway modulation in CSCs relative to non-CSCs offers a possible therapeutic opportunity. We demonstrate that treatment with the metabolic inhibitor CPI-613 (devimistat, an inhibitor of tricarboxylic acid (TCA) cycle) in vitro decreases CD133+ and CD117+ cell frequency relative to untreated OvCa cells, with negligible impact on non-CSC cell viability. Additionally, sphere-forming capacity and tumorigenicity in vivo are reduced in the CPI-613 treated cells. Collectively, these results suggest that treatment with CPI-613 negatively impacts the ovarian CSC population. Furthermore, CPI-613 impeded the unintended enrichment of CSC following olaparib or carboplatin/paclitaxel treatment. Collectively, our results suggest that CPI-613 preferentially targets ovarian CSCs and could be a candidate to augment current treatment strategies to extend either progression-free or overall survival of OvCa.

scholarly journals Metformin targets ovarian cancer stem cells in vitro and in vivo

2012 ◽  
Vol 127 (2) ◽  
pp. 390-397 ◽  
Author(s):  
Jessica J. Shank ◽  
Kun Yang ◽  
Jacob Ghannam ◽  
Lourdes Cabrera ◽  
Carolyn J. Johnston ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ovarian Cancer Stem Cells

scholarly journals RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chuanying Zhu ◽  
Keke Li ◽  
Mawei Jiang ◽  
Siyu Chen
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Xenograft Model ◽  
Clonogenic Survival ◽  
In Vivo Studies ◽  
Radiation Induced ◽  
Non Coding Rnas ◽  
Potential Strategy ◽  
Induced Apoptosis

AbstractCancer stem cells (CSCs) contribute to radioresistance in medulloblastoma. Thus, identification of key regulators of medulloblastoma stemness is critical for improving radiotherapy for medulloblastoma. In the present study, we profiled CSC-related long non-coding RNAs (lncRNAs) between radioresistant and parental medulloblastoma cells. The roles of the lncRNA RBM5-AS1 in the stemness and radiosensitivity of medulloblastoma cells were investigated. We found that RBM5-AS1, a novel inducer of medulloblastoma stemness, was significantly upregulated in radioresistant medulloblastoma cells compared to parental cells. Knockdown of RBM5-AS1 diminished the viability and clonogenic survival of both radioresistant and parental medulloblastoma cells after radiation. Silencing of RBM5-AS1 significantly enhanced radiation-induced apoptosis and DNA damage. In vivo studies confirmed that depletion of RBM5-AS1 inhibited tumor growth and increased radiosensitivity in a medulloblastoma xenograft model. In contrast, overexpression of RBM5-AS1 reduced radiation-induced apoptosis and DNA damage in medulloblastoma cells. Mechanistically, RBM5-AS1 interacted with and stabilized sirtuin 6 (SIRT6) protein. Silencing of SIRT6 reduced the stemness and reinforced radiation-induced DNA damage in medulloblastoma cells. Overexpression of SIRT6 rescued medulloblastoma cells from RBM5-AS1 depletion-induced radiosensitization and DNA damage. Overall, we identify RBM5-AS1 as an inducer of stemness and radioresistance in medulloblastoma. Targeting RBM5-AS1 may represent a potential strategy to overcome the resistance to radiotherapy in this malignancy.

ALDH1A1+ ovarian cancer stem cells co-expressing surface markers CD24, EPHA1 and CD9 form tumours in vivo

2020 ◽  
Vol 392 (1) ◽  
pp. 112009
Author(s):  
Rohit P. Nagare ◽  
Smarakan Sneha ◽  
Syama Krishnapriya ◽  
Balaji Ramachandran ◽  
Kanchan Murhekar ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Surface Markers ◽  
Ovarian Cancer Stem Cells

scholarly journals Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Nastassja Terraneo ◽  
Francis Jacob ◽  
Anna Dubrovska ◽  
Jürgen Grünberg
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Strategies ◽  
Ovarian Cancer Stem Cells ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals STEM-20. RADIO-SENSITIZING GLIOBLASTOMA CANCER STEM CELLS BY INHIBITION OF FACT

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi237-vi238
Author(s):  
Miranda Montgomery ◽  
Abigail Zalenski ◽  
Amanda Deighen ◽  
Sherry Mortach ◽  
Treg Grubb ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cancer Stem Cells ◽  
Combination Therapy ◽  
High Rate ◽  
Primary Role ◽  
Cancer Cell Growth ◽  
Treatment Paradigm

Abstract Glioblastoma (GBM) has a particularly high rate of recurrence with a 5-year overall survival rate of approximately 5%. This is in part due to a sub-population of cancer stem cells (CSC), which are both radioresistant and chemotherapeutically resistant to conventional treatments. Here we investigated CBL0137, a small molecule form of curaxin, in combination with radiotherapy as a means to radiosensitize CSCs. CBL0137 sequesters FACT (facilitates chromatin transcription) complex to chromatin, which leads to activation of p53 and inhibition of NF-κB. This sequestering of FACT results in cytotoxicity especially within tumor cells and prevents FACT from performing its primary role as a histone chaperone, as well as inhibits its part in the DNA damage response pathway. We show that when combined with radiotherapy, CBL0137 administration limited the ability of CSCs to identify and repair damaged DNA. CSCs treated in vitro with CBL0137 and irradiation showed an increased inhibition of cancer cell growth and decreased viability compared to irradiation or drug alone. Combination therapy also showed more DNA damage in the CSCs than with either agent alone. Based on our in vitro evidence for the efficacy of combination therapy to target CSCs, we moved forward to test the treatment in vivo. Using a subcutaneous model, we show that the amount of CD133+ cells (a marker for GMB CSCs) was reduced in irradiation plus CBL0137 compared to either treatment alone. Survival studies demonstrated that irradiation plus CBL0137 compared to irradiation alone or CBL0137 alone increase lifespan. Here we show the ability of CBL0137, in combination with irradiation, to target patient GBM CSCs both in vitro and in vivo. This work establishes a new treatment paradigm for GBM that inclusively targets CSCs and may ultimately reduce tumor recurrence.

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