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SLC30A9-mediated mitochondrial zinc homeostasis drives osteosarcoma chemoresistance by suppressing the mtDNA-cGAS-STING pathway
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DOI：10.1016/j.lfs.2026.124555.png)
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Abstract
En 中文
• SLC30A9 is highly expressed in chemoresistant osteosarcoma and enhances chemoresistance to MTX. • SLC30A9 facilitates mitochondrial Zinc efflux in osteosarcoma cells, thereby preserving mitochondrial function. • Knocking down SLC30A9 impairs mitochondrial Zn efflux and triggers cGAS–STING pathway activation through mtDNA leakage. • cGAS–STING pathway activation promotes NDRG1 transcription. • Combination therapy targeting SLC30A9 and STING agonist inhibits MTX-resistance in osteosarcoma.
Keywords:
OS
,
osteosarcoma
qRT-PCR
,
quantitative real-time Polymerase chain reaction
IHC
,
immunochemistry
MFI
,
mean fluorescence intensity
GSEA
,
gene set enrichment analysis
IF
,
immunofluorescence
DMSO
,
dimethyl sulfoxide
DMEM
,
Dulbecco's modified Eagle medium
TEM
,
transmission electron microscope
SLC30A9
,
solute carrier family 30 member 9
mPTP
,
mitochondrial permeability transition pore
TMRE
,
tetramethylrhodamine, ethyl ester
MitoSOX
,
mitochondrial Superoxide
ROS
,
reactive oxygen species
Calcein AM
,
calcein acetoxymethyl ester
PBS
,
phosphate buffered solution
MOMP
,
mitochondrial outer membrane permeabilization
PVDF
,
polyvinylidene fluoride
SDS
,
sodium dodecyl sulfate
RNA-seq
,
RNA-sequence
ChIP
,
chromatin immunoprecipitation
IMM
,
inner mitochondrial membrane
OMM
,
outer mitochondrial membrane
cGAMP
,
cyclic guanosine monophosphate-adenosine monophosphate
IRF3
,
interferon regulatory factor 3
NF-κB
,
nuclear factor-κB
CIN
,
chromosomal instability
DDR
,
DNA-damage response
NDRG1
,
N-Myc Downstream-Regulated Gene 1
CDNs
,
Cyclic dinucleotides
DMXAA
,
5,6-dimethylxanthenone-4-acetic acid
Osteosarcoma
Chemotherapy resistance
Mitochondria
Zn homeostasis
SLC30A9
cGAS-STING
Journal
IF:
5.1
Papers:
1.7W
Citations:
4.7W
Organization
Cited Papers