A novel long non-coding RNA GK-IT1 promotes the carcinogenesis and progression of esophageal squamous cell carcinoma via mediating the phosphorylation of MAPK1

Abstract Background: Recent studies have shown that Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of esophageal squamous cell carcinoma (ESCC). However, the biological functions and potential molecular mechanism of LncRNA GK-IT1 in esophageal squamous cell carcinoma has not been reported. Methods: We analysed the expression of GK-IT1 in ESCC and their adjacent normal tissues in the TCGA database. The quantitative real-time-PCR (qRT-PCR) was used to detect the expression of GK-IT1 in Clinical specimens. The Kaplan-Meier method was employed to draw the survival curve and then the statistical significance was calculated using the logarithmic rank test. a range of functional experiments in vivo and in vitro were used to explore the role of GK-IT1 in the carcinogenesis and development of ESCC. RNA pull down assay, RNA immunoprecipitation (RIP), fluorescence in situ hybridisation (FISH), agarose gel electrophoresis and immunofluorescence were all employed to explore the interaction mechanism between GK-IT1 and MAPK1 (mitogen activated protein kinase 1). Results: The expression of GK-IT1 was higher in ESCC than adjacent normal tissues, which was positively correlated with the clinical stage and shorter survival time. The knockout of the GK-IT1 gene significantly attenuated the abilities of ESCC cell proliferation, invasion and migration, induced apoptosis and autophagy in ESCC cells and inhibited tumour growth and tumour metastasis in vivo. on the contrary, the upregulation of GK-IT1 had the opposite effect. Further studies have shown that GK-IT1 can regulate the biological process of ESCC by regulating the phosphorylation of MAPK1. Conclusion: Our study reveals that GK-IT1 mediated the phosphorylation of MAPK1 improve the carcinogenesis and development of esophageal squamous cell carcinoma through ERK/MAPK pathway which indicates that GK-IT1 possesses substantial potential as a novel biomarker for ESCC prognosis and therapy.