Abstract 3096: LINE-1 retrotransposition L1-FGGY promotes the occurrence and progression of lung squamous cell carcinoma by inhibiting the tumor-suppressor gene FGGY

Abstract

Abstract Retrotransposition is a kind of chromatin rearrangement containing the non-coding region, which makes up about half of the human genome. Long interspersed element-1 (LINE-1) retrotransposition is the only currently known active autonomous transposon in humans and might cause genetic instability, which was reported to occur with high frequency in a variety of tumor tissues, including colon cancer, prostate cancer, ovarian cancer, hepatocellular carcinoma, etc. However, the relationship between LINE-1 and lung squamous cell carcinoma (LUSC) is unclear. In this study, we analyzed 504 cases of LUSC samples based on the RNA-seq database in The Cancer Genome Atlas (TCGA), and found that 1/3 of tumor samples possessed LINE-1 inserted retrotransposons. We screened out 14 LINE-1 retrotransposons with the highest occurrence frequency and detected the expression of LINE-1 retrotransposons in 110 clinical LUSC samples and 52 matched adjacent normal tissue samples. The results showed that among 14 screened retrotransposon genes, the expression of 13 retrotransposon genes in LUSC was significantly higher than that in the corresponding para-carcinoma tissues, indicating that the presence of LINE-1 retrotransposon was related to the occurrence of LUSC. Furthermore, by analyzing the correlationship between the expression levels of LINE-1 retrotransposons and overall survival time of patients, we also found that the survival time of patients with low retrotransposon gene expression was long, while the survival time of patients with high retrotransposon gene expression was short. Among them, L1-FGGY and L1-ATP8B1 showed significant differences. In this study, we focused on one LINE-1 retrotransposon, i.e. L1-FGGY. Then we further investigated the mechanism of the LINE-1 retrotransposition in regulating the occurrence and progression of LUSC and discovered that the expression of L1-FGGY and FGGY was negatively correlated in LUSC patients (coefficient of association=-0.232, p<0.05). In order to further explore the function of FGGY in cancer development, we constructed 3 different siRNAs which could specifically interfere with the expression of FGGY and discovered that knockdown of FGGY could promote cell proliferation, inhibit cell apoptosis, as well as facilitate cell migration and invasion in vitro. The further study showed that inhibition of FGGY could promote tumorigenesis and tumor metastasis in vivo, which collectively indicated that FGGY might function as a tumor-suppressor gene. In conclusion, we not only uncovered that the LINE-1 retrotransposition L1-FGGY promotes the development of LUSC by inhibiting the expression and function of the tumor-suppressor gene FGGY, but also revealed that LINE-1 retrotransposon might be a new biomarker for early diagnosis, prognosis evaluation, and targeted therapy in the future clinical translation. Citation Format: Rui Zhang, Jinpu Yu. LINE-1 retrotransposition L1-FGGY promotes the occurrence and progression of lung squamous cell carcinoma by inhibiting the tumor-suppressor gene FGGY [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3096.