 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 29, 2024 |
| Title |
ALKBH5 facilitates the progression of skin cutaneous melanoma through promoting ABCA1 demethylation and inhibiting autophagy in an m6A-dependent manner |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
|
| Summary |
Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM. Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-ABCA1 axis in SKCM. Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner. Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting ALKBH5 and its target ABCA1 as potential therapeutic targets in SKCM.
|
| |
|
| Overall design |
To investigate the mechanism in regulating the progression and metastasis of skin cutaneous melanoma by demethylase ALKBH5, we established A375 cell lines in which target gene has been knocked down by shRNA. We then performed RNA-Seq and MeRIP-Seq using shALKBH5 and shCtrl A375 cell line, and the comparative expression analysis data was collected.
|
| |
|
| Contributor(s) |
Wang H, Zhao S, Liu H, Liu Y, Zhang Z, Zhou Z, Wang P, Qi S, Xie J |
| Citation(s) |
38481816 |
| Submission date |
Jan 20, 2024 |
| Last update date |
Mar 20, 2024 |
| Contact name |
Julin Xie |
| E-mail(s) |
xiejulin@mail.sysu.edu.cn
|
| Organization name |
First Affiliated Hospital of Sun Yat-sen University
|
| Street address |
Zhongshan 2nd Road, Yuexiu District, Guangzhou city, Guangdong Province, China
|
| City |
Guangzhou |
| State/province |
State... |
| ZIP/Postal code |
510080 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA1067136 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253795_A375_shALKBH5VSA375_shCtrl_diffPeak_result.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE253795_A375_shALKBH5_IPVSA375_shALKBH5_input_peak.txt.gz |
4.5 Mb |
(ftp)(http) |
TXT |
| GSE253795_A375_shALKBH5_inputVSA375_shCtrl_input_Gene_differential_expression.txt.gz |
6.4 Mb |
(ftp)(http) |
TXT |
| GSE253795_A375_shCtrl_IPVSA375_shCtrl_input_peak.txt.gz |
4.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...