Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development

Liu, Yu Fan; Chiang, Shang Lun; Lin, Chien Yu; Chang, Jui‐Hsing; Chung, Chia Min; Ko, Albert Min Shan; Lin, You Zhe; Lee, Chien-Hung; Lee, Ka Wo; Chen, Mu Kuan; Hua, Chun Hung; Tsai, Ming Hsui; Chen, Yuan Chien; Ko, Ying Chin

doi:10.1038/srep24014

Cited by 34 publications

(27 citation statements)

References 37 publications

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“…When associated with Notch proteins, RBPJ acts as a transcriptional activator, but when not associated with Notch proteins, it exists in complexes with corepressors and serves to block transcription . Even though there are no studies that link RBPJ activity to laryngeal carcinoma, in 2016, Liu et al found that somatic mutations in NOTCH1 correlated strongly with higher rates of recurrence and lower survival in HNSCC. It is likely that genes that regulate Notch signalling, such as RBPJ , are in some way responsible for altering HNSCC prognosis.…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA AFAP1‐AS1/miR‐320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance

Yuan

Cheng

Song

et al. 2018

J Cellular Molecular Medi

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AFAP1‐AS1 is a long non‐coding RNA that is associated with tumorigenesis and poor prognosis in a variety of cancers. We have been suggested that AFAP1‐AS1 increases tumorigenesis in laryngeal carcinoma specifically by enhancing stemness and chemoresistance. We assessed AFAP1‐AS1 expression in human laryngeal specimens, paired adjacent normal tissues and human HEp‐2 cells. Indeed, we found not only that AFAP1‐AS1 was up‐regulated in laryngeal carcinoma specimens and cells, but also that stemness‐associated genes were overexpressed. Silencing of AFAP1‐AS1 promoted HEp‐2 cell chemoresistance under cisplatin treatment. Expression of AFAP1‐AS1 was increased in drug‐resistant Hep‐2 cells. We then probed the mechanism of AFAP1‐AS1 activity and determined that miR‐320a was a potential molecular target of AFAP1‐AS1. Luciferase reporter and qRT‐PCR assays of AFAP1‐AS1 and miR‐320a levels in human specimens and cell cultures indicated that AFAP1‐AS1 negatively regulates miR‐320a. To discover the molecular mechanism of miR‐320a, we again used the DIANA Tools algorithm to predict its genetic target, RBPJ. After cloning the 3′‐untranslated regions (3′‐UTR) of RBPJ into a luciferase reporter, we determined that miR‐320a did in fact reduce RBPJ mRNA and protein levels. Ultimately, we determined that AFAP1‐AS1 increases RBPJ expression by negatively regulating miR‐320a and RBPJ overexpression rescues stemness and chemoresistance inhibited by AFAP1‐AS1 silencing. Taken together, these results suggest that AFAP1‐AS1 can serve as a prognostic biomarker in laryngeal carcinoma and that miR‐320a has the potential to improve standard therapeutic approaches to the disease, especially for cases in which cancer cell stemness and drug resistance present significant barriers to effective treatment.

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Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA AFAP1‐AS1/miR‐320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance

Yuan

Cheng

Song

et al. 2018

J Cellular Molecular Medi

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“…Although this SNP did not cause amino acid changes, it was located in EGF-like domains of the NOTCH1 extracellular region that may play a dual role in tumorigenesis to regulate various oncogenes and tumor suppressor genes. Both overexpression and downregulation of NOTCH and ligands have been implicated in several human cancers (23)(24)(25)(26). Somatic mutations of NOTCH1 have been suggested to play an oncogenic role in breast, colorectal, and pancreatic cancers (27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

Combined Genetic Biomarkers and Betel Quid Chewing for Identifying High-Risk Group for Oral Cancer Occurrence

Chung

Lee

Chen

et al. 2017

Cancer Prevention Research

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We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case-control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in , and genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34-14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70-575.73). The synergy index was 16.58 (95% CI, 2.27-70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. .

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“…Our patient's tumor also had a functional loss of NOTCH1 . Somatic mutations in NOTCH1 have been reported in 10–15% of head and neck squamous cell carcinomas . The majority of NOTCH pathway alterations are activating mutations and a smaller subset are inactivating.…”

Section: Discussionmentioning

confidence: 99%

Pediatric laryngeal carcinoma in a heterozygous carrier of Fanconi anemia

D’Souza

Mark

DeMarcantonio

et al. 2017

Pediatric Blood & Cancer

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A case of invasive, keratinizing squamous cell carcinoma of the larynx in an 8-year-old female treated with laryngectomy is presented. Perinatal exposure to human papilloma virus and constitutional heterozygosity for a FANCC mutation were identified, though FANCC heterozygosity is not known to be cancer predisposing. An additional tumor-associated mutation in NOTCH1 was also identified potentially contributing to oncogenesis. This case illustrates an exceedingly rare type of cancer in the pediatric population and discusses diagnostic workup, evaluation of risk factors for head and neck cancer, and treatment options.

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Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development

Cited by 34 publications

References 37 publications

Long non‐coding RNA AFAP1‐AS1/miR‐320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance

Long non‐coding RNA AFAP1‐AS1/miR‐320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance

Combined Genetic Biomarkers and Betel Quid Chewing for Identifying High-Risk Group for Oral Cancer Occurrence

Pediatric laryngeal carcinoma in a heterozygous carrier of Fanconi anemia

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