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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 22, 2019 |
| Title |
Cancer stem cells associated miRNAs serve as prognostic biomarkers in colorectal cancer |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
Chemoresistance in cancer is linked to a subset of cancer cells termed “cancer stem cells” (CSCs), and in particular, those expressing the CD44 variant appear to represent a more aggressive disease phenotype. Herein, we demonstrate that CD44v6 represents a CSC population with increased resistance to chemotherapeutic agents, and its high expression is frequently associated with poor overall survival (OS) (HR:3.04; CI:1.35–6.85; p<0.001) and disease-free survival (DFS) (HR:5.30, CI:1.64–17.12, p<0.01) in CRC patients. CD44v6+ cells showed elevated resistance to chemotherapeutic drugs and significantly high tumor initiation capacity. The inhibition of CD44v6 resulted in the attenuation of self-renewal capacity and re-sensitization to chemotherapeutic agents. Of note, miRNA profiling of CD44v6+ SDCSCs identified a unique panel of miRNAs indicative of high self-renewal capacity. In particular, miR-1246 was overexpressed in CD44v6+ cells, and associated with poor OS (HR:2.44, CI:1.15–5.18, p<0.05) and DFS (HR:2.37, CI:1.03–5.44, p<0.05) in CRC patients. We demonstrate that CD44v6+ CSCs induced chemoresistance and enhance tumorigenicity in CRC cells, which is in part orchestrated by dysregulated profiles of a distinct panel of miRNAs. These findings provide a rationale for the therapeutic targeting of specific miRNAs, as well as serving as promising prognostic biomarkers in patients with colorectal neoplasia.
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| Overall design |
8 total samples, 4 CD44v6− HCT116 replicates and 4 CD44v6+ HCT116 replicates
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| Contributor(s) |
Toden S, Kunitoshi S, Cardenas J, Gu J, Hutchins E, Van Keuren-Jensen K, Uetake H, Toiyama Y, Goel A |
| Citation(s) |
30895943 |
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| Submission date |
Jan 30, 2019 |
| Last update date |
Mar 16, 2023 |
| Contact name |
Nicole Baldwin |
| E-mail(s) |
Nicole.Baldwin@BSWHealth.org
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| Organization name |
Baylor Research Institute
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| Street address |
3434 Live Oak St
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| City |
Dallas |
| ZIP/Postal code |
75204 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA517925 |
| SRA |
SRP182942 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125904_cells_miRNA_deseq2_normalized_counts.txt.gz |
23.7 Kb |
(ftp)(http) |
TXT |
| GSE125904_cells_miRNA_raw_counts.txt.gz |
12.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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