<i>N</i>‐Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth

Romano, Barbara; Pagano, Ester; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Brancaleone, Vincenzo; Lucariello, Giuseppe; Nanì, Maria Francesca; Fiorino, Ferdinando; Sparaco, Rosa; Vanacore, Giovanna; Tella, Federica Di; Cicia, Donatella; Lionetti, Ruggero; Makriyannis, Alexandros; Malamas, Michael S.; Luca, Marcello De; Aprea, Giovanni; D’Armiento, Maria; Capasso, Raffaele; Sbarro, Bernardo; Venneri, Tommaso; Marzo, Vincenzo Di; Borrelli, Francesca; Izzo, Angelo A.

doi:10.1111/bph.15737

Cited by 12 publications

(8 citation statements)

References 46 publications

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“…By removing the junctions which output by Portcullis and TopHat, we detected some consensus cancer specific novel canonical junctions that are only found by our method. We also noticed that many genes where we detected the novel junctions are related to the prostate cancer, e.g., RANBP3L (34), NAAA (35), PYROXD2 (36), etc. Taking one of our detections, the junction from SYT17, as an example.…”

Section: Resultsmentioning

confidence: 71%

novoRNABreak: local assembly for novel splice junction and fusion transcript detection from RNA-seq data

Tan

Mohanty

Liang

et al. 2022

Preprint

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We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) approaches, namely, being more sensitive in assembling novel junctions that cannot be directly aligned, and more efficient due to the strategy that focuses on junctions rather than full-length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data generated based on genome reference, as well as real RNA-seq data from breast cancer and prostate cancer samples. The results show that novoRNABreak can detect novel splice junctions and fusion transcripts efficiently with high sensitivity and reasonable specificity.

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Section: Resultsmentioning

confidence: 71%

novoRNABreak: local assembly for novel splice junction and fusion transcript detection from RNA-seq data

Tan

Mohanty

Liang

et al. 2022

Preprint

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“…The research of new therapeutic targets and methods for CRC has been the hot topic of cancer research. Among them, small molecule compounds that targeting novel CRC markers are one area where several progresses have been made [40][41][42][43][44]. In our study, RGS16, as a novel apoptosis suppressor in CRC, mainly inhibits the activation of TAK1-JNK/p38-mediated apoptosis signals through structural blocking.…”

Section: Discussionmentioning

confidence: 77%

Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling

Shen,

Yuan,

Tong

et al. 2024

Cell Death Dis

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Colorectal cancer (CRC) remains a major global cause of cancer-related mortality, lacking effective biomarkers and therapeutic targets. Revealing the critical pathogenic factors of CRC and the underlying mechanisms would offer potential therapeutic strategies for clinical application. G protein signaling (RGS) protein family modulators play essential role within regulating downstream signaling of GPCR receptors, with function in cancers unclear. Our study focused on the expression patterns of RGS proteins in CRC, identifying Regulator of G protein signaling 16 (RGS16) as a prospective diagnostic and therapeutic target. Analyzing 899 CRC tissues revealed elevated RGS16 levels, correlating with clinicopathological features and CRC prognosis by immunohistochemistry (IHC) combined with microarray. We confirmed the elevated RGS16 protein level in CRC, and found that patients with RGS16-high tumors exhibited decreased disease-specific survival (DSS) and disease-free survival (DFS) compared to those with low RGS16 expression. Functional assays demonstrated that RGS16 promoted the CRC progression, knockdown of RGS16 led to significantly increased apoptosis rates of CRC in vitro and in vivo. Notably, we also confirmed these phenotypes of RGS16 in organoids originated from resected primary human CRC tissues. Mechanistically, RGS16 restrained JNK/P38-mediated apoptosis in CRC cells through disrupting the recruitment of TAB2/TAK1 to TRAF6. This study provides insights into addressing the challenges posed by CRC, offering avenues for clinical translation.

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“…IHC analysis from the HPA was consistent with the NAAA mRNA expression discrepancy and complemented our results. Previous studies only revealed there is a relationship between NAAA expression and tumor cell progression in bladder, prostate, and colon cancer cells (28,44,45). Unfortunately, NAAA has not been largely studied in the cancer field.…”

Section: Discussionmentioning

confidence: 99%

“…Borrelli et al. ( 28 ) displayed NAAA inhibitors can induce colorectal cancer (CRC) cell cycle arrest in the S phase and reduce cell proliferation and migration. However, the potential role of NAAA in tumorigenesis and tumor progression remains fragmentary, and there are no bioinformatics analysis systematically exploring the relationship of NAAA expression between different types of human cancers.…”

Section: Introductionmentioning

confidence: 99%

Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

et al. 2022

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N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

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N‐Acylethanolamine acid amidase (NAAA) is dysregulated in colorectal cancer patients and its inhibition reduces experimental cancer growth

Abstract: Background and Purpose: N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamines (NAEs) and its pharmacological inhibition has beneficial effects in inflammatory conditions. The

Cited by 12 publications

References 46 publications

novoRNABreak: local assembly for novel splice junction and fusion transcript detection from RNA-seq data

novoRNABreak: local assembly for novel splice junction and fusion transcript detection from RNA-seq data

Regulator of G protein signaling 16 restrains apoptosis in colorectal cancer through disrupting TRAF6-TAB2-TAK1-JNK/p38 MAPK signaling

Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

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