ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation

Ning, Yichong; Hui, Na; Qing, Bei; Zhuo, Y; Sun, Wei; Du, Yan; Liu, Shunlian; Liu, Kaili; Zhou, Jianlin

doi:10.1038/s41419-019-1635-9

Cited by 24 publications

(22 citation statements)

References 29 publications

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“…Protein ubiquitylation is initiated by enzymatic cascades that involve E3 ubiquitin ligases (15). RNF180 is an E3 ubiquitin ligase that serves a key role in the function of the ubiquitin-proteasome system by determining the specificity and timing of ubiquitination and subsequent degradation of its substrates (16). RNF180 is either downregulated or absent in different types of cancer, and is regarded as a suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

Ring finger protein 180 is associated with biological behavior and prognosis in patients with non‑small cell lung cancer

Liu

Yang

et al. 2020

Oncol Lett

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There are few studies on the role of ring finger protein (RNF)180 in non-small cell lung cancer (NSCLC). The present study investigated the expression of RNF180 in NSCLC and its associations with the clinical factors and prognosis of NSCLC. The mRNA and protein expression levels of RNF180 were detected via reverse transcription-quantitative PCR and western blotting. Methylation-specific PCR (MSP) analysis was utilized to detect the methylation of RNF180. RNF180 expression levels were analyzed via immunohistochemistry. The protein and mRNA expression levels of RNF180 were lower in NSCLC cell lines compared with in the non-tumor cell line. Immunohistochemistry revealed that 64 patients that were negative for RNF180, while MSP detection analysis demonstrated that 60 patients exhibited RNF180 promoter methylation. The methylation status of RNF180 was significantly associated with RNF180 expression level. Among all factors evaluated, logistic regression analysis indicated that only T stage was significantly associated with RNF180 expression. Cox multivariate analysis demonstrated that RNF180 expression was an independent predictor of overall survival in patients with NSCLC. Methylation in the promoter of RNF180 was shown to reduce its expression levels. In summary, low RNF180 expression levels were associated with poor biological behaviors, thus RNF180 expression level may be used as a clinical marker to predict the prognosis of patients with NSCLC. Materials and methods Cell culture. NSCLC cell lines (A549 and HCC827) and a non-tumor cell line (MRC-5) were obtained from The Cell Bank of Type Culture Collection of Chinese Academy of Sciences. Cells were cultured in RPMI-1640 medium (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% FBS (HyClone; Cytiva) and 100 U/ml penicillin-streptomycin (HyClone; Cytiva) at 37˚C under a humidified atmosphere of 5% CO 2 .

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Section: Discussionmentioning

confidence: 99%

Ring finger protein 180 is associated with biological behavior and prognosis in patients with non‑small cell lung cancer

Liu

Yang

et al. 2020

Oncol Lett

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“…23 ZCCHC10 bound to and stabilized p53 by impairing the binding relation between p53 and MDM2, and the p53 inhibitor pifithrin-α weakened the impacts of ZCCHC10 restoration on p53 pathway, cell cycle and apoptosis in lung cancer. 24 Our data demonstrated that specific inhibition of p53 by The data was performed as means ± SD of three independent experiments. One-way ANOVA was used to compare the mean of samples among multiple groups, followed by Tukey's multiple comparisons test.…”

Section: Dovepressmentioning

confidence: 51%

<p>The Anti-Apoptotic Role of EBV-LMP1 in Lymphoma Cells</p>

Zeng¹,

Chen²,

Jia³

et al. 2020

CMAR

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Background: Epstein-Barr virus (EBV) has been indicated in the development of some tumors, including lymphoma. However, the potential role of latent membrane protein 1 (LMP1) encoded by EBV in the tumorigenesis of lymphoma remains debated. Herein, we examined the function of LMP1 in lymphoma. Methods: The expression of LMP1 was downregulated or upregulated in EBV negative cell line SNT-8 and positive cell line KHYG-1, respectively. Subsequently, the cell viability, apoptosis, as well as the expression patterns of p53, mouse double minute 2 (MDM2), B-cell CLL/lymphoma 2 (Bcl-2) and NF-κB were evaluated. Next, the binding relationship between MDM2 and p53 along with p53 ubiquitination in cells was tested by Western blot and coimmunoprecipitation. Finally, the effects of LMP1 on lymphoma cell growth through p53, Bcl-2 and NF-κB pathways were verified by functional rescue experiments. Results: Overexpression of LMP1 promoted KHYG-1 cell growth and inhibited cell apoptosis. Moreover, LMP1 upregulation significantly enhanced the activation of NF-κB pathway, thus increasing MDM2 binding to p53, leading to p53 ubiquitination and degradation as well as Bcl-2 expression enhancement. Further inhibition of the NF-κB pathway or Bcl-2 expression significantly weakened the promotive role of LMP1 in the growth of KHYG-1 cells. Conclusion: EBV-LMP1 promoted the p53 ubiquitination and degradation by activating NF-κB signaling pathway and the following binding of MDM2 and p53 in cells to enhance Bcl-2 expression, thus promoting the growth of lymphoma cells and inhibiting cell apoptosis.

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“…MDM2, as a negative regulator of p53, can bind to p53 to limit its function, and ubiquitinate p53 to promote degradation 22–24 . MDM2 maintains the tumor characteristics of lung cancer via suppressing the function and expression levels of p53 43–46 . For example, Cai et al .…”

Section: Discussionmentioning

confidence: 99%

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

et al. 2020

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Background HS‐1‐associated protein‐1 (HAX1) has been reported to be overexpressed in non‐small cell lung cancer (NSCLC) tissues. However, the underlying mechanism of HAX1 in NSCLC has not previously been demonstrated. The present study investigated the role and underlying mechanism of HAX1 in NSCLC. Methods The HAX1 expression were confirmed in NSCLC tissues through TCGA database and qRT‐PCR. Moreover, we performed qRT‐PCR, Western blotting, Transwell assays, TUNEL assays and so on to evaluate the role of HAX1 in A549 and H1299 cell lines. Results mRNA expression of HAX1 was overexpressed in NSCLC tissues compared to adjacent normal tissues according to The Cancer Genome Atlas (TCGA) database. QRT‐PCR assays showed that HAX1 mRNA expression was upregulated in NSCLC tissues. The high HAX1 mRNA levels were found to be positively associated with tumor size, TNM stage and lymphatic metastasis. Silencing of HAX1 promoted apoptosis and reduced invasion of A549 and H1299 cells by inhibiting the AKT/mTOR and MDM2/P53 signal pathway. AKT agonist SC79 could inhibit apoptosis and promote proliferation, migration and invasion of A549 and H1299 cells transfected with si‐HAX1. Conclusions The present study provided a better understanding of HAX1 mechanism in NSCLC and potential therapeutic target for NSCLC.

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ZCCHC10 suppresses lung cancer progression and cisplatin resistance by attenuating MDM2-mediated p53 ubiquitination and degradation

Cited by 24 publications

References 29 publications

Ring finger protein 180 is associated with biological behavior and prognosis in patients with non‑small cell lung cancer

Ring finger protein 180 is associated with biological behavior and prognosis in patients with non‑small cell lung cancer

<p>The Anti-Apoptotic Role of EBV-LMP1 in Lymphoma Cells</p>

HAX1 enhances the survival and metastasis of non‐small cell lung cancer through the AKT/mTOR and MDM2/p53 signaling pathway

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