Autophagy suppression enhances DNA damage and cell death upon treatment with PARP inhibitor Niraparib in laryngeal squamous cell carcinoma

Ji, Yunxiang; Wang, Qian; Zhao, Qian; Zhao, Song; Li, Li; Sun, Guangbin; Ye, Li

doi:10.1007/s00253-019-10148-y

Cited by 11 publications

(17 citation statements)

References 45 publications

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“…Autophagy plays complex roles in HNSCC. Further investigation to elucidate the roles and clarify the mechanisms of autophagy in HNSCC is imperative ( 32 – 34 ). The analyses conducted in the current study suggest that autophagy-related lncRNAs may provide novel insights into the prediction of HNSCC prognoses.…”

Section: Discussionmentioning

confidence: 99%

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

et al. 2021

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Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson’s correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

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Section: Discussionmentioning

confidence: 99%

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

et al. 2021

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“…Recently, growing evidence has indicated the potential relationship between autophagy and LSCC. Autophagy suppression was reported to enhance DNA damage and cell death of LSCC cells [13]. LncRNA H19 were found to regulate the autophagy-related drug resistance in LSCC by targeting miR-107 [37].…”

Section: Discussionmentioning

confidence: 99%

“…The targeted inhibition of autophagy-related pathway has been shown to exert curative effect on many tumors [10][11][12]. The anti-tumor effect of autophagy suppression has also been reported in LSCC, indicating its crucial function in the progression of this disease [13,14].…”

Section: Introductionmentioning

confidence: 99%

An Autophagy-related Long Non-coding RNA Prognostic Signature for Laryngeal Squamous Cell Carcinoma

Shen

Huang

et al. 2021

Preprint

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Background: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in the head and neck. Considering the role of autophagy in tumor development and drug resistance, we investigated the potential prognostic value of autophagy-related long no-coding RNAs (lncRNAs) in LSCC patients. Methods: Autophagy-related lncRNAs were screened out based on the Cancer Genome Atlas (TCGA) database. Subsequently, five autophagy-related lncRNAs with prognostic value were identified through univariate and multivariate Cox regression analysis. Based on these prognosis-related lncRNAs, a risk signature was established, and the patients with LSCC were divided into the low- and high-risk groups. Finally, a nomogram based on the prognosis signature was constructed. Results: The overall survival time of the high-risk group was significantly shorter than that of the low-risk one (p<0.0001). Receiver operating characteristic curve (ROC) analysis was performed to further confirm the validity of the model (ROC of training set: 0.841, ROC of test set: 0.718, ROC of entire set: 0.757). Univariate and multivariate regression analyses demonstrated that ours is an independent prognosis signature of LSCC. The nomogram integrating the five-lncRNA signature and clinical factors was then constructed for clinical application. Conclusion: In summary, our signature of the five autophagy-associated lncRNAs can serve as an effective prognostic indicator for patients with LSCC.

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“…The other PARP1 substrates involved in this process remain to be revealed in targeted proteomic screens. The combination of PARPi therapy with autophagy inhibition may also act synergistically, as demonstrated with the PARPi niraparib in laryngeal squamous carcinoma cells [ 86 ].…”

Section: Parps In Hallmark Cancer Traitsmentioning

confidence: 99%

The PARP Enzyme Family and the Hallmarks of Cancer Part 1. Cell Intrinsic Hallmarks

Demény

Virág

2021

Cancers

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The 17-member poly (ADP-ribose) polymerase enzyme family, also known as the ADP-ribosyl transferase diphtheria toxin-like (ARTD) enzyme family, contains DNA damage-responsive and nonresponsive members. Only PARP1, 2, 5a, and 5b are capable of modifying their targets with poly ADP-ribose (PAR) polymers; the other PARP family members function as mono-ADP-ribosyl transferases. In the last decade, PARP1 has taken center stage in oncology treatments. New PARP inhibitors (PARPi) have been introduced for the targeted treatment of breast cancer 1 or 2 (BRCA1/2)-deficient ovarian and breast cancers, and this novel therapy represents the prototype of the synthetic lethality paradigm. Much less attention has been paid to other PARPs and their potential roles in cancer biology. In this review, we summarize the roles played by all PARP enzyme family members in six intrinsic hallmarks of cancer: uncontrolled proliferation, evasion of growth suppressors, cell death resistance, genome instability, reprogrammed energy metabolism, and escape from replicative senescence. In a companion paper, we will discuss the roles of PARP enzymes in cancer hallmarks related to cancer-host interactions, including angiogenesis, invasion and metastasis, evasion of the anticancer immune response, and tumor-promoting inflammation. While PARP1 is clearly involved in all ten cancer hallmarks, an increasing body of evidence supports the role of other PARPs in modifying these cancer hallmarks (e.g., PARP5a and 5b in replicative immortality and PARP2 in cancer metabolism). We also highlight controversies, open questions, and discuss prospects of recent developments related to the wide range of roles played by PARPs in cancer biology. Some of the summarized findings may explain resistance to PARPi therapy or highlight novel biological roles of PARPs that can be therapeutically exploited in novel anticancer treatment paradigms.

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Autophagy suppression enhances DNA damage and cell death upon treatment with PARP inhibitor Niraparib in laryngeal squamous cell carcinoma

Cited by 11 publications

References 45 publications

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

An Autophagy-related Long Non-coding RNA Prognostic Signature for Laryngeal Squamous Cell Carcinoma

The PARP Enzyme Family and the Hallmarks of Cancer Part 1. Cell Intrinsic Hallmarks

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