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RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC)
Chen, Pengchen1,2,3; Wang, Wei1; Wong, Sin Wa1; Li, Junnan1; Wu, Qiushaung1; Zhang, Shu Dong4; Lin, Yao5; Kwok, Hang Fai1,2
2022-12-01
Source PublicationCell Death Discovery
Volume8Issue:1
Abstract

Gastric neuroendocrine carcinoma (GNEC) is a common type of neuroendocrine carcinoma (NEC) with a poor prognosis and limited therapeutic options. The underlying mechanisms of chemoresistance in patients with GNEC and those with NEC are largely unknown, and thus, reliable biomarkers and therapeutic targets that could improve treatment outcomes in patients with NECs are lacking. The aim of this study was to identify specific targets and investigate their roles in GNEC progression and treatment resistance. Differentially expressed genes (DEGs) were identified in GNEC specimens and were further analysed by focusing on their roles in chemoresistance. Gene Ontology (GO) and pathway enrichment analyses of GNEC DEGs revealed that synapse-related function was the most prominent cellular function perturbed in GNEC. SNAP25 was identified as the target gene involved in most of the enriched pathways. In vitro and in vivo experiments showed that SNAP25 plays a role in proliferation and chemoresistance in GNEC cell lines. AKT has been identified as a downstream target, and SNAP25 binds to AKT protein and promotes AKT protein half-life. Further analysis of other types of NEC as well as small cell lung cancer, which resembles NEC on a molecular level, has identified RUNDC3A as an upstream molecule that regulates SNAP25 expression and the associated phenotypes that could enhance chemoresistance in NECs. Our results show that SNAP25 expression in GNEC is mediated by RUNDC3A and promotes GNEC progression and chemoresistance via posttranslational modification of AKT. Thus, our results suggest that the RUNDC3A/SNAP25/Akt axis could be a potential therapeutic target in GNEC.

DOI10.1038/s41420-022-01084-4
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000815638500002
Scopus ID2-s2.0-85132900158
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionMinistry of Education Frontiers Science Center for Precision Oncology, University of Macau
Faculty of Health Sciences
Cancer Centre
Animal Research Core
Corresponding AuthorLin, Yao; Kwok, Hang Fai
Affiliation1.Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, SAR, Macao
2.MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, SAR, Macao
3.Centre for Reproductive Medicine, Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Guangzhou, China
4.Northern Ireland Centre for Stratified Medicine, Ulster University, Londonderry, Northern Ireland, United Kingdom
5.Central Laboratory of the Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Collaborative Innovation Center for Rehabilitation Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, China
First Author AffilicationCancer Centre;  University of Macau
Corresponding Author AffilicationCancer Centre;  University of Macau
Recommended Citation
GB/T 7714
Chen, Pengchen,Wang, Wei,Wong, Sin Wa,et al. RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC)[J]. Cell Death Discovery,2022,8(1).
APA Chen, Pengchen,Wang, Wei,Wong, Sin Wa,Li, Junnan,Wu, Qiushaung,Zhang, Shu Dong,Lin, Yao,&Kwok, Hang Fai.(2022).RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC).Cell Death Discovery,8(1).
MLA Chen, Pengchen,et al."RUNDC3A regulates SNAP25-mediated chemotherapy resistance by binding AKT in gastric neuroendocrine carcinoma (GNEC)".Cell Death Discovery 8.1(2022).
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