Fbxo22 promotes cervical cancer progression via targeting p57Kip2 for ubiquitination and degradation

Lin, Min; Zhang, Jianan; Bouamar, Hakim; Wang, Zhi-wei; Sun, Lu; Zhu, Xueqiong

doi:10.1038/s41419-022-05248-z

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…The slices were washed by PBS three times, and incubated with the relevant secondary antibody for 45 min. Then, IHC were conducted as described previously [ 22 ]. The human tissue study was approved by the ethical committee of the Second Affiliated Hospital of Wenzhou Medical University.…”

Section: Methodsmentioning

confidence: 99%

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

Mei,

Pan,

Huang

et al. 2024

Discov Onc

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Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

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Section: Methodsmentioning

confidence: 99%

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

Mei,

Pan,

Huang

et al. 2024

Discov Onc

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“…Western blot experiments were performed as previously [ 67 ]. Anti-SRGN (1:100, sc-374657, Santa Cruz Biotechnology), Anti-HIST1H1C (1:1000, ab4086, abcam), Anti-APOE (1:1000, #13366, Cell Signaling Technology), anti-Tubulin (1:5000, #T0023, Affinity Biosciences) and anti-β-Actin (1:4000, #T0022, Affinity Biosciences) were used as primary antibodies.…”

Section: Methodsmentioning

confidence: 99%

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

Sheng,

Pan,

et al. 2024

Cell Death Dis

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Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell–cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

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“…F-box protein is a subunit of SCF E3 ligase complexes and has been characterized to involve in numerous biological functions in human cancer, such as apoptosis, invasion, cell cycle, proliferation, autophagy, drug resistance, EMT, cancer stem cells and metastasis (31)(32)(33)(34). SCF E3 ligase consists of adaptor SKP1, scaffold Cullin-1, RBX1 or RBX2 and F-box protein.…”

Section: F-box Proteinsmentioning

confidence: 99%

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

et al. 2023

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The tumor microenvironment (TME) is the tumor surrounding environment, which is critical for tumor development and progression. TME is also involved in clinical intervention and treatment outcomes. Modulation of TME is useful for improving therapy strategies. PD-L1 protein on tumor cells interacts with PD-1 protein on T cells, contributing to T cell dysfunction and exhaustion, blockage of the immune response. Evidence has demonstrated that the expression of PD-1/PD-L1 is associated with clinical response to anti-PD-1/PD-L1 therapy in cancer patients. It is important to discuss the regulatory machinery how PD-1/PD-L1 protein is finely regulated in tumor cells. In recent years, studies have demonstrated that PD-1/PD-L1 expression was governed by various E3 ubiquitin ligases in TME, contributing to resistance of anti-PD-1/PD-L1 therapy in human cancers. In this review, we will discuss the role and molecular mechanisms of E3 ligases-mediated regulation of PD-1 and PD-L1 in TME. Moreover, we will describe how E3 ligases-involved PD-1/PD-L1 regulation alters anti-PD-1/PD-L1 efficacy. Altogether, targeting E3 ubiquitin ligases to control the PD-1/PD-L1 protein levels could be a potential strategy to potentiate immunotherapeutic effects in cancer patients.

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Fbxo22 promotes cervical cancer progression via targeting p57Kip2 for ubiquitination and degradation

Cited by 11 publications

References 33 publications

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

DDOST is associated with tumor immunosuppressive microenvironment in cervical cancer

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis

The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy

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