normal tissues. Increased expression of 3 L1 retrotransposons (L1-FGGY, L1-ATP8P1 and L1-SVEP1) was significantly associated with poor clinical outcome, large tumor size, central location or smoking history. Among these three, the L1-FGGY occurred frequently in LUSC tumors (38%, 19 out of 50 LUSC cases) and it promoted cell proliferation and invasion, inhibited cell apoptosis, as well as facilitated tumorigenesis in vitro and vivo. Increased L1-FGGY expression in tumors was coupled with decreased expression of FGGY gene, implicating the L1 insertion into FGGY disrupted the expression and function of the tumor-suppressor gene. Lastly, we observed that the reverse transcription inhibitors, nevirapine (NVR) and efavirenz (EFV) dramatically suppressed L1-FGGY expression and elevated FGGY expression, therefore inhibited the proliferation and invasion of L1-FGGY positive LUSC cells both in vitro and vivo. Conclusion: In conclusion, L1-FGGY retrotransposition was a frequent genomic event in LUSC that promoted the development and progression of LUSC and could be a novel prognosis marker and potential therapeutic target for LUSC.
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