LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY.

Somatic long interspersed element-1 () retrotransposition is a genomic process that relates to gene disruption and tumor occurrence. However, the expression and function of retrotransposition in lung squamous cell carcinoma (LUSC) remain unclear. We analyzed the transcriptomes of LUSC samples in The Cancer Genome Atlas and observed retrotransposition in 90% of tumor samples. Thirteen retrotranspositions of high occurrence were identified and further validated from an independent Chinese LUSC cohort. Among them, ( was identified as the most frequent retrotransposition in the Chinese cohort and significantly correlated with poor clinical outcome. occurred with smoke-induced hypomethylation of the promoter and contributed to the development of local immune evasion and dysfunctional metabolism. Overexpression of or knockdown of promoted cell proliferation and invasion , facilitated tumorigenesis , and dysregulated cell energy metabolism and cytokine/chemotaxin transcription. Importantly, specific reverse transcription inhibitors, nevirapine and efavirenz, dramatically countered abundance, inhibited tumor growth, recovered metabolism dysfunction, and improved the local immune evasion. In conclusion, hypomethylation-induced expression is a frequent genomic event that promotes the development and progression of LUSC and represents a promising predictive biomarker and therapeutic target in LUSC. SIGNIFICANCE: is a prognosis predictive biomarker and potential therapeutic target to overcome local immune evasion in lung squamous cell carcinoma.