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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 03, 2022 |
| Title |
Investigation of target molecule alterations by a cDNA microarray in CU27-treated HCC cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND & AIMS: Growing lines of evidence suggests that a subpopulation of cancer cells with self-renewal and tumor-initiating capacity, termed as cancer stem cells (CSCs) or tumor initiation cells (TICs), play pivotal roles in tumor relapse and tumor distant organ metastasis. Therefore, to prevent and treat metastasis based on targeting essential molecules regulating CSCs emerges a promising strategy. Here we describe CU-27, a novel organic selenium compound, significantly diminishes hepatocarcinoma cancer cell (HCC) stemness and inhibits cacner cell metastasis in vitro and in vivo. METHODS: we performed a functional screen to identify compounds with anti-CSC and metastasis effects, In vitro CSC models, tumorspheres, drug resistance and the flow cytometry analysis of CSC markers together were used. In vivo CSC models, limiting dilution and metastatic mouse model were used. We compared mRNA expression profiles of the CU27-treated and control cells with mRNA microarray. The key biological target of CU27 was analyzed by Ingenuity pathway analysis (IPA). The surface plasmon resonance (SPR), chromatin immunoprecipition (ChIP) assays and the dual luciferase reporter assays were used to explore mechanisms of CU27. RESULTS: A novel selenium-containing small molecule-CU-27, was demonstrated to significantly inhibit CSCs self-renewal and function as a metastasis suppressor of HCC cells in vitro and in vivo. Through differentially expressed gene screening with cDNA microarray and IPA analysis, c-MYC, which is mostly recognized to play very important roles in tumor initiation and maintenance in many kinds of tumors, was identified as the major biological target of CU-27. CU-27 was found to significantly suppress c-MYC transcription function and downregulate expression levels of its target genes, thereby inhibit CSC self-renewal and distant metastasis of HCC cells. Ectopic expression of c-MYC rescues the inhibition effects of CU-27 on HCC cells. More important, CU-27 was further demonstrated to interact directly with the bHLH domain of c-MYC protein and decrease its occupancy of the promoter region of target genes, which, in turn, downregulates c-MYC target gene expressions. CONCLUSIONS: CU-27 which can inhibit HCC CSCs and distant metastasis through suppressing c-MYC transcriptional function. Our study provides a vital strategy for targeting CSC and metastasis by inhibiting c-MYC function with novel selenium-containing small molecules.
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| Overall design |
The profiles of differentially expressed mRNAs were analyzed in Hep3b cells and Huh7.5.1 cells treated with 10 μM CU27 (48 hours) or DMSO as controls.
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| Contributor(s) |
Zhou J, Zhang B, Wang H, Yue W, Pei X |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 03, 2019 |
| Last update date |
Nov 04, 2022 |
| Contact name |
Jun-Nian Zhou |
| E-mail(s) |
hcoohboy@163.com
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| Organization name |
Institute of Health Service and Transfusion Medicine
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| Lab |
Stem Cell and Regenerative Medicine
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| Street address |
27# Taiping Road
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| City |
Beijing |
| ZIP/Postal code |
100850 |
| Country |
China |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (8)
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| GSM3746620 |
hep3b HCC cells_DMSO treated (48h), biological rep2 |
| GSM3746621 |
hep3b HCC cells_DMSO treated (48h), biological rep3 |
| GSM3746622 |
hep3b HCC cells_CU27 treated (48h), biological rep2 |
| GSM3746623 |
hep3b HCC cells_CU27 treated (48h), biological rep3 |
| GSM3746624 |
Huh7.5.1 HCC cells_DMSO treated (48h), biological rep1 |
| GSM3746625 |
Huh7.5.1 HCC cells_DMSO treated (48h), biological rep2 |
| GSM3746626 |
Huh7.5.1 HCC cells_CU27 treated (48h), biological rep1 |
| GSM3746627 |
Huh7.5.1 HCC cells_CU27 treated (48h), biological rep2 |
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| Relations |
| BioProject |
PRJNA540934 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130666_RAW.tar |
15.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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