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Digestive Diseases and Sciences

Digestive Diseases and Sciences

IF: 2.5
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E3 Ubiquitination Ligase MYLIP Mediates the NKRF/SLC25A34 Axis to Suppress Malignant Progression in Colorectal Cancer

Published:11 December 2024 DOI: 10.1007/s10620-024-08735-9 PMID: 39661280
Chao Li,?Gang Yu,?Wanjing Chen,?Jijie Ouyang,?Xiaoshan Wang,?Zhengguang Wang

Abstract

Background: The SLC25 family of transport proteins has been implicated in colorectal cancer (CRC) tumorigenesis. However, the potential role of SLC25A34 in CRC remains unclear. This study was designed to elucidate the role and mechanism of SLC25A34 in CRC.

Methods: By screening differentially expressed genes in the GSE141174 and GSE184093 datasets and colorectal adenocarcinoma in the GEPIA database, we identified SLC25A34 as an important gene in CRC. Expression of SLC25A34, NKRF, and MYLIP in CRC cells was examined by RT-qPCR and?western blot analysis. CCK-8, colony formation, TUNEL, and Transwell assays were used to detect CRC cell proliferation, growth, mobility, and apoptosis. Mice were injected subcutaneously or intravenously to explore the effects of MYLIP, NKRF, and SLC25A34 on xenograft formation and lung metastasis. The underlying molecular mechanisms were further investigated using RT-qPCR, western blot, immunoprecipitation, protein stability, and ubiquitination assays.

Results: SLC25A34 was reduced in CRC tissues and cells, and overexpression of SLC25A34 repressed the malignant phenotype of CRC cells. NKRF inhibited SLC25A34 transcription in CRC cells, and silencing SLC25A34 overturned the suppressive effects of NKRF knockdown on cell proliferation, growth, and mobility. Overexpression of MYLIP in CRC cells inhibited NKRF expression by degrading NKRF to activate SLC25A34 transcription and inhibit xenograft formation and lung metastases.

Conclusion: Our study revealed a novel role for MYLIP-mediated NKRF ubiquitination and degradation in the induction of SLC25A34 transcription, which may act as a therapeutic target for CRC.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Crystal Violet 548-62-9 C25H30ClN3 761 suppliers $5.00-$2070.00
Hematoxylin 517-28-2 C16H14O6 438 suppliers $5.00-$6710.00
Eosin Disodium 17372-87-1 C20H6Br4Na2O5 408 suppliers $8.00-$1270.00
Phenylmethylsulfonyl fluoride 329-98-6 C7H7FO2S 407 suppliers $5.00-$2530.00
MG-132 133407-82-6 C26H41N3O5 292 suppliers $11.00-$1000.00
PUROMYCIN 53-79-2 C22H29N7O5 91 suppliers $73.60-$1200.00

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