APE1 promotes proliferation and migration of cutaneous squamous cell carcinoma

Deng, Xian-Yu; Zhen, Peilin; Niu, Xinli; Dai, Yu; Wang, Yinghui; Zhou, Meijuan

doi:10.1016/j.jdermsci.2020.08.012

Cited by 17 publications

(11 citation statements)

References 33 publications

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“…It is also con rmed that knowing down APE1 in the LUAD cells inhibited their proliferation, invasion and migration, while overexpressing APE1 had the opposite effects. This is consistent with some studies showing that overexpression of APE1 promotes epithelia-mesenchymal transition (EMT) of cervical cancer and cutaneous squamous cell carcinoma cells [28,29]. The similar results have been reported for NSCLC [30].…”

Section: Discussionsupporting

confidence: 93%

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

Zhou

Wei

Yang

et al. 2023

Preprint

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Background: Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cell homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. Nevertheless, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. Methods: The up-regulated expression gene APE1 that was screened out through differential expression analysis of biogenic data and RNA-seq results. The q-PCR experiments and immunohistochemical these two techniques were used to detect its expression both in lung adenocarcinoma and normal lung tissues. The effect of APE1 on the proliferation was determined by two experiments as CCK-8 and EdU. The Transwell and scratch tests were both used to evaluate the invasion and migration ability. The effect of APE1 on DNA damage and radiotherapy sensitivity was determined by clonal formation, immunofluorescence and flow cytometry. Through biogenic analysis and enrichment of APE1 related molecules and pathways, the regulation of APE1 on STING and its downstream signaling pathways was verified by western blot. In addition, APE1 directly interacts with AIM2 and DDX41 detected by RNA-seq and co-immunoprecipitation to inactivate the interferon gene stimulating factor (STING) pathway, thereby inhibiting pyroptosis after radiotherapy. The effect of APE1 on tumor occurrence and radiotherapy in vivo was observed in nude mouse model. Results: The expression level of APE1 was significantly increased in LUAD and can promote the activity levels of proliferation, migration and invasion in LUAD cells. APE1 plays an anti-radiation role by regulating STING pathway through DDX41. APE1 can induce pyroptosis of cells after radiotherapy through AIM2; APE1 can promote tumor generation, enhance tumor load and inhibit radiosensitivity in vivo. Conclusions: APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. could induce pyroptosis and negatively regulate by interaction with AIM2 and DDX41. APE1 inhibitors should be considered for enhancing the radiosensitivity of LUAD cells and improving patient prognosis and therapeutic outcomes. Thus, APE1 may play a role in affecting tumor immune microenvironment and tumor immunotherapy.

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Section: Discussionsupporting

confidence: 93%

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

Zhou

Wei

Yang

et al. 2023

Preprint

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“…In recent years, it has been found that a variety of novel molecules are involved in the occurrence and development of cSCC and as functions of promoting tumor formation through a variety of signaling pathways, such as apurinic/apyrimidinic endonuclease 1 (APE1) 22 , DEAD-box helicase 46 (DDX46) 23 , targeting protein for Xenopus kinesin-like protein 2 (TPX2) 24 , kynureninase (KYNU) 25 , signal transducer and activator of transcription 3 (STAT3) 26 , histone deacetylase 3 (HDAC3) 27 , SAM- and SH3-domain containing 1 gene (SASH1) 28 , karyopherin subunit alpha 4 (KPNA4) 29 , ephrin B receptor 2 (EphB2) 30 , and cell division cycle 20 (CDC20) 31 . APE1 has been reported to be significant high regulated in tumor tissues of human cSCC patients, and its high expression promoted the proliferation and migration of cSCC cells 22 . DDX46 was obvious upregulated in human cSCC tissues and cells, it was found that DDX46 knockdown resulted in the suppression of cell proliferation, and the activation of cell apoptosis and autophagy, suggested DDX46 maybe a novel potential therapeutical target of cSCC 23 .…”

Section: Discussionmentioning

confidence: 99%

PRR14 acts a novel oncogene activating the PI3K signal pathway in human cutaneous squamous cell carcinoma

Zhang¹,

Yang²,

Ji³

et al. 2023

J. Cancer

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Proline rich protein 14 (PRR14) is considered as a new component of the nuclear fiber layer, it may be a key molecule in mediating nuclear morphological changes and functional changes in tumorigenesis. But, it's still unclear in human cutaneous squamous cell carcinoma (cSCC). In the study, the expression profiles of PRR14 in patients with cSCC were investigated by immunohistochemistry (IHC), also the PRR14 expression in cSCC tissues were detected using the methods of real-time quantitative PCR (RT-qPCR) and Western blot; cell counting kit-8 (CCK-8) assay, wound healing assay, matrigel-based transwell assay and Annexin V-FITC and PI double-staining with flow cytometry assay were used to investigate the biological functions of PRR14 in A431 and HSC-1 cSCC cells. Overexpression of PRR14 in cSCC patients was reported firstly in this study and its high expression was related to differentiation, thickness and tumor node metastasis (TNM) stage of cSCC. PRR14 inhibition with RNA interfering (RNAi) method resulted in the suppression of cell proliferation, migration and invasion but promotion the apoptosis of cSCC cells, and upregulation of the protein phosphorylation levels of mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K) and Akt. The study shows PRR14 maybe an activator of cSCC carcinogenesis through PI3K/Akt/mTOR signal pathway, and it also maybe a prognostic factor and new therapeutical target for cSCC treatment.

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“…Ape1/Ref-1 is composed of 2 functionally different subunits, Ape1 and Ref-1, which can form a highly conserved functional complex after integration. It is involved in the occurrence and progression of a variety of malignant tumors (14,15). Ionizing radiation can cause lung tissue cells to be in a state of intense oxidative stress and promote the compensatory synthesis of Ape1/Ref-1, thereby regulating the level of cellular oxidative stress transcription factors (16,17).…”

Section: Discussionmentioning

confidence: 99%

Clinical value of serum Ape1/Ref-1 combined with TGF-β1 monitoring in predicting the occurrence of radiation pneumonitis (RP) in non-small cell lung cancer patients

Zhang¹,

You²,

Duan³

et al. 2021

Ann Palliat Med

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Background:The aim of the present study was to explore the predictive value of serum apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) combined with transforming growth factor β1 (TGF-β1) levels in the occurrence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLS).Methods: Eighty-one patients with NSCLS who were admitted from August 2017 to July 2019 were enrolled in the present study. All patients were treated with concurrent radiotherapy and chemotherapy.Serum Ape1/Ref-1 and TGF-β1 levels were measured before treatment and 12 weeks after treatment.Patients with radiation-induced lung injury were assessed and divided into the RP group (lung injury ≥2) and non-RP (NRP) group (grade <2). The levels of serum Ape1/Ref-1 and TGF-β1 before and after treatment between the 2 groups were compared. The relationship between clinical characteristics, serum Ape1/Ref-1, TGF-β1 levels, and the occurrence of RP were then analyzed, and the relationship between serum Ape1/ Ref-1, TGF-β1 levels, and their predictive value for the occurrence of RP was also assessed. Results:The incidence of RP in 81 patients was 30.86%. After treatment, the serum Ape1/Ref-1 and TGF-β1 levels of the 2 groups were significantly higher than those before treatment (P<0.05). Furthermore, after treatment, the levels of serum Ape1/Ref-1 and TGF-β1 in the RP group were significantly higher than those of the NRP group (P<0.05). Multivariate logistic regression analysis showed that V20, Ape1/Ref-1, and TGF-β1 were associated with the occurrence of RP (P<0.05). The levels of serum Ape1/Ref-1 were positively correlated with TGF-β1 (r=0.734, P<0.05). Finally, the area under the curve of RP occurrence, which was predicted by the levels of serum Ape1/Ref-1, TGF-β1, and the combination of both were 0.779, 0.69, and 0.842, respectively. Conclusions:The occurrence of RP in NSCLS patients is closely related to the levels of serum Ape1/Ref-1 and TGF-β1, and the combination of both has important predictive values for the occurrence of RP.

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APE1 promotes proliferation and migration of cutaneous squamous cell carcinoma

Cited by 17 publications

References 33 publications

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

PRR14 acts a novel oncogene activating the PI3K signal pathway in human cutaneous squamous cell carcinoma

Clinical value of serum Ape1/Ref-1 combined with TGF-β1 monitoring in predicting the occurrence of radiation pneumonitis (RP) in non-small cell lung cancer patients

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