China Oncology ›› 2024, Vol. 34 ›› Issue (6): 537-547.doi: 10.19401/j.cnki.1007-3639.2024.06.002
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DONG Jianqiao1(), LI Kunyan1, LI Jing2, WANG Bin2, WANG Yanhong3, JIA Hongyan2(
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Received:
2024-03-07
Revised:
2024-06-07
Online:
2024-06-30
Published:
2024-07-16
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DONG Jianqiao, LI Kunyan, LI Jing, WANG Bin, WANG Yanhong, JIA Hongyan. A study on mechanism of SIRT3 inducing endocrine drug resistance in breast cancer via deacetylating YME1L1[J]. China Oncology, 2024, 34(6): 537-547.
Fig. 2
SIRT3 is highly expressed in tamoxifen-resistant breast cancer. A: SIRT3 mRNA expression was detected by RTFQ-PCR. B, C: SIRT3 protein expression and quantification in both cell lines were detected by Western blot. *: P<0.05, compared with each other; ***: P<0.001, compared with each other."
Fig. 3
Detection of mitochondrial morphology and function in breast cancer after endocrine resistance A, B: Mitochondrial length was observed and quantified by fluorescence staining (scale bar=5 μm); C, D: Mitochondrial morphology was observed and quantified by transmission electron microscopy (scale bar=200 nm); E, F: Western blot was used to detect and quantify L-OPA1 protein in parental cells and drug-resistant cells. G, H: DHE staining assessment, ROS levels and quantification in parental and resistant cells (scale bar=200 μm). *: P<0.05, compared with each other; **: P<0.01, compared with each other."
Fig. 4
Cell proliferation, mitochondrial morphology, and function were examined by SIRT3 knockdown in drug-resistant cells A, B, C: Western blot was used to detect the expression and quantification of SIRT3 protein and L-OPA1 protein after SIRT3 knockdown. D: CCK-8 assay was used to detect the cell viability under tamoxifen treatment; E, G: DHE probe was used to detect the intracellular ROS level and quantification after SIRT3 knockdown (scale bar=200 μm); F, H: Immunofluorescence detection of mitochondrial length changes and quantification after SIRT3 knockdown (scale bar=5 μm). *: P<0.05, Si-NC compared with Si-SIRT3."
Fig. 5
Overexpression of SIRT3 in parental cells examined cell proliferation, mitochondrial morphology, and function A, B, C: Western blot was used to detect the expression and quantification of L-OPA1 protein after SIRT3 overexpression; D: After SIRT3 was overexpressed in parental cells, CCK-8 assay was used to detect the cell viability under tamoxifen treatment; E, G: Detection and quantification of mitochondrial membrane potential by JC-1 probe (scale bar=200 μm); H, I: Fluorescence staining for mitochondrial morphology and quantification (scale bar=5 μm). *: P<0.05, compared with each other; **: P<0.01, compared with each other; ***: P<0.001, compared with OE-SIRT3 group."
Fig. 6
Changes in mitochondrial morphology caused by overexpression of YME1L1 in parental cells A, B: YME1L1 was overexpressed, and the expression and quantification of L-OPA1 protein were detected by Western blot. C, D: Length and quantification of mitochondria by fluorescent staining (scale bar=5 μm). **: P<0.01, compared with each other; ***: P<0.001, compared with YME1L1-K237Q."
Fig. 7
SIRT3 regulates the acetylation status of YME1L1 A-G: IP was used to detect the interaction between YME1L1 and SIRT3 and quantify. *: P<0.05, compared with each other; **: P<0.01, compared with each other; ***: P<0.001, compared with each other. H: Co-localization of YME1L1 and SIRT3 was detected by immunofluorescence (scale bar=50 μm)."
Fig. 8
Deacetylating Y ME1L1 promotes tamoxifen resistance in breast cancer CCK-8 assay was used to detect cell viability under tamoxifen treatment. *: P<0.05, compared with each other; **: P<0.01, compared with each other; ***: P<0.001, compared with each other. ns: No significance, compared with YME1L1-WT or YME1L1-K237R."
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