Notch signaling in oral pre-cancer and oral cancer

Nigam, Kumud; Srivastav, Ratnesh Kumar

doi:10.1007/s12032-021-01593-9

Cited by 6 publications

(4 citation statements)

References 114 publications

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“…Using miRNA to lower the expression of ADAM10 inhibited the NOTCH pathway, and ultimately up-regulated the sensitivity of malignant tumor cells against tumor drugs. Yang et al2019 showed that repressing the expression of ADAM17 in HCC cells by miR-3163 enhanced the sensitivity of HCC cells to molecular targeted agents 28 . Conversely, studies investigating γ-secretase, which mediates the second step of Notch cleavage is also of great significance 25 .…”

Section: Discussionmentioning

confidence: 99%

“…In this process, the activation of the Notch pathway is mainly dependent on the cleavage of the Notch protein: when the Notch protein is cleaved, the extracellular and intracellular segments of the Notch protein separate to release the intracellular products, which migrate into the nucleus and ultimately mediate the expression of factors related to cell survival and anti-apoptosis [25,26]. The activation of Notch protein is a two-step cleavage, process in which the first cleavage is completed by two ADAMs: ADAM17 and ADAM10 [27][28][29]. This makes ADAM17 or ADAM10 an ideal intervention target for the treatment of malignant tumors.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

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miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng

Wang

et al. 2022

J. Cancer

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Background:The Notch pathway, which is related to the drug-resistance of lung adenocarcinoma (LUAD) type of non-small cell lung cancer (NSCLC) cells, is activated by cleavage of Notch proteins mediated by ADAMs, ADAM10 or ADAM17. Methods: In the present study, our results demonstrated that of these two ADAMs, the expression of ADAM10 in clinical samples of the LUAD type of NSCLC was much higher than that of ADAM17, while miR-140-3p -an miRNA that could target ADAM10 -was identified by an online tool: miRDB (miRNA database). The detail function and mechanism of miR-140-3p in regulating the sensitivity of NSCLC cells to antitumor drugs was systematically explored in vitro and in vivo. Results: In A549, a typical NSCLC LUAD cell line, miR-140-3p decreased ADAM10 expression and repressed activation of the Notch pathway by repressing cleavage of Notch proteins. The expression of miR-140-3p was negatively related to ADAM10 in clinical specimens. Nucleocytoplasmic separation/ subfraction assays showed that miR-140-3p was able to inhibit the cleavage of Notch protein, and led to the accumulation of Notch intracellular domains (NICD) in the nucleus. Overexpression of miR-140-3p enhanced the sensitivity of A549 cells to antitumor agents by targeting the 3'UTR region of ADAM10 mRNA in both cultured cells and in vivo models. Conclusion: ADAM10 plays a major role in LUAD, and miR-140-3p acts on ADAM10 and inhibits its expression and the cleavage of Notch protein, leading to the inhibition the activity of the Notch pathway, and ultimately upregulating LUAD cell sensitivity to anti-tumor drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Ivyspring International Publishermentioning

confidence: 99%

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Meng

Wang

et al. 2022

J. Cancer

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“…These interactions are critical for cellular differentiation and homeostasis. Dysregulation may contribute to abnormal cell fate decisions and disrupted tissue morphogenesis [30].…”

Section: Notch1 Mutations In Relation To Developmental Dynamics Of Or...mentioning

confidence: 99%

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Shafi,

Aakash,

Haseeb

et al. 2024

Preprint

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Background: Oral Squamous Cell Carcinoma (OSCC) poses a global health challenge, demanding an in-depth understanding of its mutational landscape. The complex mutational profile underscores the need for targeted therapies. OSCC's impact on crucial functions necessitates precise interventions for improved patient outcomes. This investigation into OSCC's mutational landscape through developmental biology aims to fill critical knowledge gaps, contributing possibly towards future personalized therapies and advancing our approach to this challenging malignancy. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate the mutational landscape of OSCC through the lens of developmental dynamics. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate OSCC oncogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study into Oral Squamous Cell Carcinoma (OSCC) reveals a complex genetic landscape marked by mutations in key regulators including TP53, CASP8, CDKN2A, FAT1, PIK3CA, and RYR2. TP53 emerges as a central player, with mutations disrupting its tumor-suppressive functions and influencing developmental processes in OSCC. Dysregulated Notch1 signaling contributes to aberrant cell differentiation and tissue morphogenesis. JAK/STAT and SHH signaling, essential for normal oral epithelial development, exhibit dual dynamics in OSCC, influencing both normal developmental processes and tumorigenesis. Implications for precision medicine arise from the identified genetic alterations, offering potential targets for future therapeutic interventions. Notch1 and TP53 signaling pathways emerge as promising targets, while modulating JAK/STAT and SHH signaling presents challenges and opportunities for new therapeutic strategies. Conclusion: This study reveals genetic complexities and regulatory networks disrupted in OSCC carcinogenesis and also playing key roles in developmental dynamics of oral squamous epithelium. Key genes like TP53 and Notch1, integral to oral epithelial development, undergo dysregulation, influencing OSCC initiation. JAK/STAT and SHH signaling, crucial in normal development, exhibit dual roles, contributing to OSCC progression. This study also points to targeted therapeutic strategies that may emerge in future by investigating OSCC through developmental dynamics. Further research may provide deeper insights into the complex developmental biology, paving the way for enhanced interventions in OSCC.

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“…In recent years, alterations in signaling pathways involved in OC have been shown to be important factors affecting OC development [ 15 , 16 ]. Among them, the canonical mitogen-activated protein kinase (MAPK) signaling pathway is considered to be involved in the growth and development of most cells [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

lncRNA DLEU2 Accelerates Oral Cancer Progression via miR-30a-5p/RAP1B Axis to Regulate p38 MAPK Signaling Pathway

Zhang

Wang

et al. 2022

Disease Markers

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Background. Oral cancer (OC) is common cancer in the world. Long noncoding RNAs (lncRNAs) have been shown to be involved in cancer regulation, including oral cancer (OC). The aim of this study was to investigate the role of lncRNA deleted in lymphocytic leukemia 2 (DLEU2) in oral cancer. Method. The Gene Expression Omnibus database was used to analyze differentially expressed lncRNA/microRNA (miRNA, miR)/mRNA. The expression levels of DLEU2, miR-30a-5p, and RAP1B in OC cells were detected by RT-qPCR. Dual-luciferase was used to analyze the binding of lncRNA/miRNA/mRNA. Cell Counting Kit-8 was used to measure cell proliferation. Transwell assay was used to inspect cell migration and invasion abilities. Western blot was used to detect MAPK pathway-related protein levels. Result. Our research shows that, in contrast to miR-30a-5p, DLEU2 or RAP1B was upregulated in OC cells, and high expression of DLEU2 or RAP1B was associated with poorer overall survival. Inhibiting the expression of DLEU2 slowed the proliferation and reduced the ability of migration and invasion of Tca8113 and CAL-27 cells. miR-30a-5p was predicted to interact with DLEU2 or RAP1B by bioinformatics, and dual-luciferase analysis confirmed this interaction. Notably, si-DLEU2 suppressed RAP1B expression and protein level, and after overexpression of RAP1B in OC cells, reversal of suppressed DLEU2 expression was observed. Furthermore, the inhibitory effect of si-DLEU2 on MAPK signaling was reversed by overexpression of RAP1B. Therefore, si-DLEU2 regulates MAPK signaling through the miR-30a-5p/RAP1B axis and inhibits OC development. Conclusion. DLEU2 contributed to proliferation, migration and invasion via miR-30a-5p/RAP1B axis to regulate MAPK signaling pathway in OC cells.

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Notch signaling in oral pre-cancer and oral cancer

Cited by 6 publications

References 114 publications

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

lncRNA DLEU2 Accelerates Oral Cancer Progression via miR-30a-5p/RAP1B Axis to Regulate p38 MAPK Signaling Pathway

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