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A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma

ABSTRACT: A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma

PROVIDER: PRJNA834064 | ENA |

REPOSITORIES: ENA

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A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma

Project description:Cisplatin resistance is one of the main causes of treatment failure and death of head and neck squamous cell carcinoma (HNSCC). In order to better understand the mechanism of cisplatin resistance and formulate effective treatment strategies, we identified differentially expressed genes related to cisplatin resistance by RNA sequencing, RT-PCR and immunoblotting. CREB5 was selected as the most significantly up-regulated gene in cisplatin resistant cells. Gain- and loss-of-function experiments were performed to detect the effect of CREB5 on cisplatin resistance and mitochondrial apoptosis in HNSCC. Chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay, and immunoblotting experiments were performed to explore the underlying mechanisms of CREB5.

2022-07-07 | GSE202030 | GEO

A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma.

Project description:BackgroundCisplatin resistance is one of the main causes of treatment failure and death in head and neck squamous cell carcinoma (HNSCC). A more comprehensive understanding of the cisplatin resistance mechanism and the development of effective treatment strategies are urgent.MethodsRNA sequencing, RT-PCR, and immunoblotting were used to identify differentially expressed genes associated with cisplatin resistance. Gain- and loss-of-function experiments were performed to detect the effect of CREB5 on cisplatin resistance and mitochondrial apoptosis in HNSCC. Chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay, and immunoblotting experiments were performed to explore the underlying mechanisms of CREB5.ResultsCREB5 was significantly upregulated in cisplatin-resistant HNSCC (CR-HNSCC) patients, which was correlated with poor prognosis. CREB5 overexpression strikingly facilitated the cisplatin resistance of HNSCC cells in vitro and in vivo, while CREB5 knockdown enhanced cisplatin sensitivity in CR-HNSCC cells. Interestingly, the activation of AKT signaling induced by cisplatin promoted nucleus translocation of CREB5 in CR-HNSCC cells. Furthermore, CREB5 transcriptionally activated TOP1MT expression depending on the canonical motif. Moreover, CREB5 silencing could trigger mitochondrial apoptosis and overcome cisplatin resistance in CR-HNSCC cells, which could be reversed by TOP1MT overexpression. Additionally, double-targeting of CREB5 and TOP1MT could combat cisplatin resistance of HNSCC in vivo.ConclusionsOur findings reveal a novel CREB5/TOP1MT axis conferring cisplatin resistance in HNSCC, which provides a new basis to develop effective strategies for overcoming cisplatin resistance.

| S-EPMC9248137 | biostudies-literature

RNA-seq of human head and neck cancer cell line SQD9 knock-out for TMEM45A exposed to cisplatin

Project description:Human head and neck squamous cell carcinoma, SQD9 cells, were stable invalidated for TMEM45A using shRNA (Sigma). Then, transduced SQD9 cells were treated with 100 µM of cisplatin during 24h. All conditions were compared to untreated cells transduced with shRNA control (shCTL)(Sigma).

2020-03-04 | E-MTAB-7518 | biostudies-arrayexpress

Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance

Project description:In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, BAG-1 (Bcl-2 associated athanogene-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression. Advanced HNSCC cells revealed resistant to cisplatin accompanied by increased expression of BAG-1 protein. siRNA knockdown of BAG-1 expression resulted in significant improvement of HNSCC sensitivity to cisplatin. BAG-1 expression enhanced stability of BCL-xL and conferred cisplatin resistant to the HNSCC cells. In addition, high levels of expression of phospho AKT, BAG-1, and BCL- xL were observed in advanced HNSCC compared to in that of primary HNSCC. Conclusion: Increased expression of BAG-1 was associated with cisplatin resistance and tumor progression in HNSCC patients and warrants further validation in larger independent studies. Over expression of BAG-1 may be a biomarker for cisplatin resistance in patients with primary or recurrent HNSCCs and targeting BAG-1 could be helpful in overcoming cisplatin resistance.

2017-10-04 | GSE102787 | GEO

Gene profile for chemotherapy response in head and neck carcinoma

2013-10-06 | GSE32877 | GEO

Elucidating miRNA associated with cisplatin resistance in head and neck cancer cells

Project description:Elucidating miRNA associated with cisplatin resistance in head and neck cancer cells

| PRJNA533083 | ENA

Gene profile for chemotherapy response in head and neck carcinoma

Project description:Transcriptional profiling was performed on biopsies from patients with head and neck squamous cell carcinoma that had been treated with cisplatin and 5-fluorouracil to identify genes predictive of response to chemotherapy Two condition experiment, Biopsies from complete clinical responders and from non-responders were compared based upon a common reference using a two color design

2013-10-06 | E-GEOD-32877 | biostudies-arrayexpress

Global miRNA expression profile of head and neck squamous cell carcinoma patients with resistant and sensitive tumors

Project description:The aim of the present study was to evaluate miRNAs as response predictors in FFPE head and neck samples from a phase II clinical trial designed to evaluate the feasibility of delivering cisplatin concurrent with radiotherapy after an induction chemotherapy (IC) regimen based on the combination of cisplatin plus paclitaxel in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. For this purpose, we assessed the global miRNA expression profile of 15 HNSCC patients undergoing treatment, in order to identify miRNAs able to segregate resistant tumors from the sensitive ones, thus serving as markers to predict response. The results showed four miRNAs (miR-21, miR-494, miR-720 and miR-923) that were overexpressed in HNSCC FFPE samples.

2016-10-25 | E-MTAB-4854 | biostudies-arrayexpress

Elucidating miRNA associated with cisplatin resistance in head and neck cancer cells

Project description:To investigate the function of the three microRNAs involved in drug resistance in head and neck cancer, we transfected them into oral squamous cancer cell line, SAS. The phenotypes were analyzed and transcriptome of them were investigated.

2020-02-01 | GSE129875 | GEO

Long noncoding RNA lnc-POP1-1 upregulated by VN1R5 promotes cisplatin resistance in head and neck squamous cell carcinoma through interaction with MCM5

Project description:Cisplatin resistance is a major therapeutic challenge in advanced head and neck squamous cell carcinoma (HNSCC). Here, we aimed to investigate the key signaling pathway for cisplatin resistance in HNSCC cells. HNSCC cell lines that were sensitive (HN4 and HN30) or resistant (HN4/DDP and HN30/DDP) to cisplatin were used for this study. Moreover, the cisplatin-resistant human melanoma cell lines (A375/DDP) and human lung cancer cell lines (A549/DDP) have also been established. To identify the role of proteins in the acquisition of cisplatin resistance, we analyzed the abnormally expressed protein via protein mass spectrometry methods (isobaric tags for relative and absolute quantitation, iTRAQ) in cisplatin-sensitive and cisplatin-resistant cancer cells, and found that VN1R5 was highly expressed in cisplatin-resistant cells. Long noncoding RNA lnc-POP1-1 upregulated by VN1R5. To deeply investigate the mechanism by which lnc-POP1-1 affects cisplatin resistance in HNSCC cells, we used RNA pull-down assays followed by mass spectrometry to explore the putative RNA-binding proteins (RBPs) interacting with lnc-POP1-1.

2020-11-28 | PXD022799 |

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