LNX1 Contributes to Cell Cycle Progression and Cisplatin Resistance

Abstract

The ligand of numb-protein X1 (LNX1) acts as a proto-oncogene by inhibiting p53 stability; however, the regulation of LNX1 expression has not been investigated. In this study, we screened chemicals to identify factors that potentially regulate LNX1 expression. We found that LNX1 expression levels were decreased by DNA damage, including that by cisplatin. Upon treatment with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA), LNX1 expression levels increased. In addition, cell-cycle progression increased upon LNX1 expression; the levels of S and G2/M populations were correlated with LNX1 expression. Moreover, in CRISPR-Cas9-mediated LNX1 knockout cells, we observed a delay in cell-cycle progression and a downregulation of genes encoding the cell-cycle markers cyclin D1 and cyclin E1. Finally, the upregulation of LNX1-activated cell-cycle progression and increased resistance to cisplatin-mediated cell death. Taken together, these results suggest that LNX1 contributes to cell-cycle progression and cisplatin resistance.

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“…SRPX2 has also been shown to confer chemoresistance for 5-Fu and gemcitabine by activating the PI3K/AKT axis in pancreatic cancer [ 47 ]. LNX1 has been shown to contribute to cisplatin resistance by regulating cell cycle progression in human cancer cells [ 48 ]. For all these genes, epigenetic modulation of gene expression involved in chemoresistance has not been elucidated.…”