MUC15 is an independent prognostic factor that promotes metastases of MYCN non-amplified neuroblastoma
© The author(s)..
Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
|---|---|
| Enthalten in: |
Journal of Cancer - 14(2023), 18 vom: 01., Seite 3496-3507 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Guo, Huiqin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Revised 01.12.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.7150/jca.89360 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365123080 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365123080 | ||
| 003 | DE-627 | ||
| 005 | 20231226101015.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.7150/jca.89360 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1217.xml |
| 035 | |a (DE-627)NLM365123080 | ||
| 035 | |a (NLM)38021164 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Guo, Huiqin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MUC15 is an independent prognostic factor that promotes metastases of MYCN non-amplified neuroblastoma |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 01.12.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © The author(s). | ||
| 520 | |a Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a MUC15 | |
| 650 | 4 | |a MYCN non-amplified | |
| 650 | 4 | |a MYCT1 | |
| 650 | 4 | |a metastases | |
| 650 | 4 | |a neuroblastoma | |
| 700 | 1 | |a Zhang, Wei-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qiu-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hai-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jiabin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuo, Zhenjian |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Miao, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Huimin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of Cancer |d 2010 |g 14(2023), 18 vom: 01., Seite 3496-3507 |w (DE-627)NLM201575388 |x 1837-9664 |7 nnns |
| 773 | 1 | 8 | |g volume:14 |g year:2023 |g number:18 |g day:01 |g pages:3496-3507 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.7150/jca.89360 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 14 |j 2023 |e 18 |b 01 |h 3496-3507 | ||