Bioinformatics Studies Provide Insight into Possible Target and Mechanisms of Action of Nobiletin against Cancer Stem Cells

Hermawan, Adam; Putri, Herwandhani

doi:10.31557/apjcp.2020.21.3.611

Cited by 11 publications

(10 citation statements)

References 64 publications

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“…Our GCP model consists of 9 prognostic genes which could be regarded as promising therapeutic targets for precision treatment in GC. There are plenty of experimental evidences have suggested that some of these 9 genes including DDX24 [ 39 , 40 ], TTF2 [ 14 , 15 ], SSX4 [16] , ACLY [41] , [42] , [43] , [44] , VPS35 [45] , [46] , [47] , [48] , DCTN2 [49] , [50] , [51] , [52] and MRPL4 [ 53 , 54 ] played important roles in development and progression in many tumor types. However, there was few report about ARGLU1 functions in cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

et al. 2021

eBioMedicine

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Background Due to the molecular mechanism complexity and heterogeneity of gastric cancer (GC), mechanistically interpretable biomarkers were required for predicting prognosis and discovering therapeutic targets for GC patients. Methods Based on a total of 824 GC-specific fitness genes from the Project Score database, LASSO—Cox regression was performed in TCGA-STAD cohort to construct a GC Prognostic (GCP) model which was then evaluated on 7 independent GC datasets. Targets prioritization was performed in GC organoids. ARGLU1 was selected to further explore the biological function and molecular mechanism. We evaluated the potential of ARGLU1 serving as a promising therapeutic target for GC using patients derived xenograft (PDX) model. Findings The 9-gene GCP model showed a statistically significant prognostic performance for GC patients in 7 validation cohorts. Perturbation of SSX4, DDX24, ARGLU1 and TTF2 inhibited GC organoids tumor growth. The results of tissue microarray indicated lower expression of ARGLU1 was correlated with advanced TNM stage and worse overall survival. Over-expression ARGLU1 significantly inhibited GC cells viability in vitro and in vivo. ARGLU1 could enhance the transcriptional level of mismatch repair genes including MLH3, MSH2, MSH3 and MSH6 by potentiating the recruitment of SP1 and YY1 on their promoters. Moreover, inducing ARGLU1 by LNP-formulated saRNA significantly inhibited tumor growth in PDX model. Interpretation Based on genome-wide functional screening data, we constructed a 9-gene GCP model with satisfactory predictive accuracy and mechanistic interpretability. Out of nine prognostic genes, ARGLU1 was verified to be a potential therapeutic target for GC. Funding National Natural Science Foundation of China.

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Section: Discussionmentioning

confidence: 99%

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

et al. 2021

eBioMedicine

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“…Subcellular localization analysis was performed with Wolfpsort subcellular localization predication software 36 . GO, KEGG pathway and domain enrichment analyses were carried out by DAVID tool with corrected p-value below 0.05 37 . The two-tailed Fisher’s exact test was applied to check the Khib proteins.…”

Section: Methodsmentioning

confidence: 99%

“…The two-tailed Fisher’s exact test was applied to check the Khib proteins. Multiple testing correction was performed using the Benjamini–Hochberg false discovery rate (FDR) control method 37 . The images of the significantly pathways were obtained from KEGG.…”

Section: Methodsmentioning

confidence: 99%

Global analysis of lysine 2-hydroxyisobutyrylation in wheat root

Wang

et al. 2021

Sci Rep

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Lysine 2-hydroxyisobutyrylation (Khib) is a novel naturally occurring post-translational modification. The system Khib identification at proteomics level has been performed in various species and tissues to characterize the role of Khib in biological activities. However, the study of Khib in plant species is relatively less. In the present study, the first plant root tissues lysine 2-hydroxyisobutyrylome analysis was performed in wheat with antibody immunoprecipitation affinity, high resolution mass spectrometry-based proteomics and bioinformatics analysis. In total, 6328 Khib sites in 2186 proteins were repeatedly identified in three replicates. These Khib proteins showed a wide subcellular location distribution. Function and pathways characterization of these Khib proteins indicated that many cellular functions and metabolism pathways were potentially affected by this modification. Protein and amino acid metabolism related process may be regulated by Khib, especially ribosome activities and proteins biosynthesis process. Carbohydrate metabolism and energy production related processes including glycolysis/gluconeogenesis, TCA cycle and oxidative phosphorylation pathways were also affected by Khib modification. Besides, root sulfur assimilation and transformation related enzymes exhibited Khib modification. Our work illustrated the potential regulation role of Khib in wheat root physiology and biology, which could be used as a useful reference for Khib study in plant root.

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“…These studies highlight the potential of NOB in disease treatment and its protective effects. The newly published articles have shed some light on the capability of NOB in cancer therapy [80,81]. In the present review, we attempt to mechanistically examine the efficiency of NOB in cancer therapy by focusing on molecular pathways and mechanisms.…”

Section: Therapeutic and Biological Activities Of Nobmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.

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Bioinformatics Studies Provide Insight into Possible Target and Mechanisms of Action of Nobiletin against Cancer Stem Cells

Cited by 11 publications

References 64 publications

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

Global analysis of lysine 2-hydroxyisobutyrylation in wheat root

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

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