Dataset Information

Expression of the long noncoding RNA RP11-169D4.1-001 in Hypopharyngeal Squamous cell carcinoma tissue and its clinical significance.

ABSTRACT: BACKGROUND:Increased research efforts have demonstrated that lncRNAs are associated with multiple head and neck tumors and play important roles in cancer. We previously found that RP11-169D4.1-001 plays a tumor-suppressive role in laryngeal cancer, but its function in human hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Thus, this research aimed to analyze the relationship between RP11-169D4.1-001 expression and HSCC clinicopathological features. METHODS:Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of RP11-169D4.1-001 in 70 pairs of HSCC and adjacent normal tissues. RESULTS:The expression level of RP11-169D4.1-001 in HSCC tissues was significantly lower than that in adjacent normal tissues (P = .001). The expression of RP11-169D4.1-001 had no significant relationship with tumor differentiation, stage, smoking, drinking, age, tumor location, or treatment. RP11-169D4.1-001 expression was associated with T category (P = .008) and lymph node metastasis (P = .001). Survival data were assessed by Kaplan-Meier curves. Patients with high RP11-169D4.1-001 expression were found to have a shorter overall survival than patients with low RP11-169D4.1-001 expression. Multivariate analysis also indicated that target RNA was an independent factor for prognosis. The ROC curve was constructed to clarify the diagnostic value of RP11-169D4.1-001. CONCLUSIONS:RP11-169D4.1-001 may serve as a new biomarker and potential drug target and can be used as a new biomarker and a potential drug target for the detection and treatment of hypopharyngeal cancer, respectively. Furthermore, RP11-169D4.1-001 expression may be an independent prognostic factor affecting the survival of hypopharyngeal cancer patients.

SUBMITTER: Shen Z

PROVIDER: S-EPMC6977134 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Expression of the long noncoding RNA RP11-169D4.1-001 in Hypopharyngeal Squamous cell carcinoma tissue and its clinical significance.

Shen Zhisen Z Wu Linrong L Hao Wenjuan W Li Qun Q Zhou Chongchang C

Journal of clinical laboratory analysis 20190911 1

<h4>Background</h4>Increased research efforts have demonstrated that lncRNAs are associated with multiple head and neck tumors and play important roles in cancer. We previously found that RP11-169D4.1-001 plays a tumor-suppressive role in laryngeal cancer, but its function in human hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Thus, this research aimed to analyze the relationship between RP11-169D4.1-001 expression and HSCC clinicopathological features.<h4>Methods</h4>Real-time ...[more]

PMID: 31512299

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Project description:BackgroundLong noncoding RNAs (lncRNAs) are implicated in the oncogenesis and metastasis of multiple human cancers. Nonetheless, the precise molecular mechanisms underlying the oncogenic role of lncRNA in esophageal squamous cell carcinoma (ESCC) remains to be clarified.MethodsThe expression of GK intronic transcript 1 (GK-IT1) was analyzed using ESCC RNA-seq data from The Cancer Genome Atlas database. Quantitative real-time PCR was used to measure the expression of GK-IT1 in ESCC clinical samples and cells. The correlation between GK-IT1 expression and clinicopathological variables was examined using chi-squared tests. Kaplan-Meier survival and Cox regression analyses were employed to generate the survival curve and assess the prognostic value of GK-IT1. Functional experiments were utilized to explore the role of GK-IT1 in promoting cell migration, invasion, proliferation, and suppressing apoptosis and autophagy in ESCC. To understand the mechanism, an RNA pulldown assay, RNA immunoprecipitation, agarose gel electrophoresis, immunofluorescence, and co-immunoprecipitation assays were used.ResultsIn this study we identified an unreported lncRNA, termed GK-IT1 that was aberrantly overexpressed in ESCC tissues and cells. GK-IT1 was closely associated with advanced clinical stage, and it was an independent prognostic indicator of ESCC. Functional assays verified that GK-IT1 significantly promoted ESCC proliferation, invasion, and migration, and suppressed ESCC apoptosis and autophagy. Furthermore, tumorigenesis experiments in nude mice indicated that GK-IT1 promoted ESCC tumor growth and metastasis. Mechanistically, GK-IT1 competitively bound to mitogen-activated protein kinase 1 (MAPK1) to prevent the interaction between dual specificity phosphatase 6 (DUSP6) and MAPK1, thereby controlling the phosphorylation of MAPK1 and promoting ESCC progression.ConclusionOur study revealed that GK-IT1 competed with DUSP6 to attenuate the interaction between DUSP6 and MAPK1, leading to activation of the ERK/MAPK pathway, thereby promoting progression of ESCC. Our research indicated that GK-IT1 served as a novel potential target for the diagnosis and treatment of ESCC.

Project description:Purpose:The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking. Methods:PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 in HSCC was characterized. In vitro assays including cell viability assays, migration assays, invasion assays as well as Western blot assays were performed to illuminate the biological functions and underlying molecular mechanisms of PD-L1 in HSCC development. Results:PD-L1 expression was detected in HSCC samples but we found no positive expression in matched normal hypopharyngeal mucosal tissues. The levels of PD-L1 expression were significantly correlated with advanced clinical progression and poor patient survival. Multivariable analysis of Cox model showed that PD-L1 expression was an independent predictor for the prognosis of HSCC patients. Functional experiments showed that the ectopic expression of PD-L1 markedly influenced the proliferation, migration and invasion of FaDu cells in vitro. Mechanistically, investigations demonstrated that PD-L1 could promote the epithelial-mesenchymal transition of FaDu cells. Meanwhile, PD-L1 knockdown inhibited, while PD-L1 overexpression activated the Akt-mTOR signaling pathway in FaDu cells. The EMT induced by PD-L1 overexpression could be reversed by the Akt inhibitor. Conclusion:In summary, the expression of PD-L1 can act as a significant biomarker for the adverse clinicopathological features and poor prognosis of patients with HSCC. PD-L1 can promote the proliferation, migration and invasion of FaDu cells and consequently enhance the aggressiveness. Moreover, PD-L1 induces EMT through AKT-mTOR signaling pathway. These suggest that PD-L1 has important tumor-intrinsic functions independent of its immunopathogenic effects.

Dataset Information

Expression of the long noncoding RNA RP11-169D4.1-001 in Hypopharyngeal Squamous cell carcinoma tissue and its clinical significance.

Publications

Expression of the long noncoding RNA RP11-169D4.1-001 in Hypopharyngeal Squamous cell carcinoma tissue and its clinical significance.

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