Background & objectivesLUC7L2 may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. However, their detailed features and regulatory mechanisms of LUC7L2 in the development of human liver cancer have not been well characterized. ResultsHerein, our results demonstrate that LUC7L2 promotes the proliferation of liver cancer cells in vitro and xenograft transplantation in vivo. The proliferation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (24th hour: P = 0.00043; 48th hour: P = 0.000017). The cellular colony formation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (25.18±6.94 % vs 67.63±9.57 %, P = 0.00009). The weight of transplanted tumors was significantly increased in the rLV-LUC7L2 group compared to rLV group (0.387±0.074 vs 0.958± 0.103 g, P = 0.00004). Moreover, LUC7L2 effects on epigenetic regulation based on H3K4me3 in human liver cancer cells. e,g, RRAS. Furthermore, LUC7L2 affects transcriptome and proteome in liver cancer. In particular, LUC7L2 enhances the modification ability of H3K4me3and RNAPolII on the promoter region of RRAS and then enhances the expression of RRAS in liver cancer. Strikingly, LUC7L2 increases the increases the DNA damage repair ability dependent on RRAS. Although the DNA damage repair ability was significantly increased in the rLV-LUC7L2 group compared to rLV group(1.868±0.181 vs 0.17±0.034, P = 0.0000022), it was not significantly changed in rLV-LUC7L2+rLV-shRNA RRAS group compared with rLV group(1.868±0.181 vs 1.798±0.313, P = 0.317). Importantly, LUC7L2 enhances the carcinogenic function dependent on RRAS. In particular, RRAS increased the DNA damage repair ability by enhancing the formation of DNA damage repair dependent on tri-methylation of histone H3 lysine 36 (H3K36me3). ConclusionsIt is implied that LUC7L2's role in liver cancer proliferation is largely dependent on RRAS. The first discovery provides a basis for the prevention and treatment of human liver cancer.
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