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| Status |
Public on Mar 09, 2023 |
| Title |
Increased retinoic acid signalling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway [RNA-seq_KD] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
MYB-NFIB fusion and NOTCH1 mutation are hallmark genetic events familiar in SACC that promote lung metastasis. However, abnormal expression of MYB and NOTCH1 was also observed in without MYB-NFIB fusion and NOTCH1 mutation. Here, through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation, we explore in-depth the molecular mechanisms of lung metastasis. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near normal to cancer state based on the normal tissue occupancy for each cell cluster. In this context, we identified the Notch signalling pathway enrichment in almost all cancer cells; trajectory and sub-clustering analyses investigated deeply cancer progenitor-like cell clusters in primary tumour-associated lung metastases, in which signature genes enriched in the ‘MYC_TARGETS_V2’ gene set. In vitro, we detected the complexes of the NICD1-MYB-MYC by Co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) signalling as endogenous antagonists of the ‘MYC_TARGETS_V2’ gene set. Following this, we validate that all-trans retinoic acid (ATRA) reduces the lung metastasis in SACC via correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic and immunohistochemical (IHC) analyses of four primary tissues and eleven metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of diagnosis and treatment of the RA system.
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| Overall design |
We performed RNA-seq analysis of cells exposed to different treatments or conditions, including ATRA, NOTCH1 and/or MYB knockdown (MYB_KD and NICDKD and Double_KD), and MYB overexpression (MYBCDNA); these data are available in the Dr.Tom system (Beijing Genomics Institute, BGI).
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| Contributor(s) |
Zhou M, Yang J |
| Citation(s) |
36879115 |
| |
| Submission date |
Nov 02, 2022 |
| Last update date |
Mar 09, 2023 |
| Contact name |
kong lu |
| E-mail(s) |
konglu@ccmu.edu.cn
|
| Organization name |
ccmu
|
| Street address |
capital medical university
|
| City |
peking |
| ZIP/Postal code |
100086 |
| Country |
China |
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| Platforms (1) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE216852 |
Increased retinoic acid signalling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway |
|
| Relations |
| BioProject |
PRJNA896910 |
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