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Regulation of Cell Motility by La-Related Protein 4 in Ovarian Cancer Cell

MAHY NABIL MAHMOUD EGIZ 東北大学

2020.03.25

概要

The La-related proteins (LARPs) are a family of RNA binding proteins that modulate the degradation and stabilization of RNAs. Multiple studies implicated the dysregulation of LARPs in cancer progression. Cell motility is known to potentiate the metastatic potential of ovarian cancer cells. However, the roles of LARPs in cell motility remain unknown. In the present study, we investigated the roles of LARPs in the progression of ovarian cancer using SKOV3 human ovarian cancer cells and a public database that integrates microarray-based gene expression data and clinical data. To explore the involvement of LARPs in the cell motility, we performed RNA interference screening for LARPs in SKOV3 cells. The screening identified LARP4 as a potential suppressor of the formation of lamellipodia. Conversely, enforced expression of LARP4 suppressed the formation of lamellipodia. Moreover, cell migration was significantly increased in LARP4-knocked-down SKOV3 cells. Mechanistically, LARP4 knock-down was associated with the increase in RhoA protein expression. These results suggest that LARP4 may limit RhoA-dependent cell motility. In a mouse xenograft model with SKOV3 cells, the peritoneal metastasis was increased with LARP4 knock- down increased. Upon analysis of a public database of patients with ovarian cancer, the LARP4 mRNA-high expression group (n = 166) showed longer overall survival compared with the LARP4 mRNA-low expression group (n = 489), implying a positive correlation of LARP4 mRNA levels in ovarian cancer tissues with patient prognosis. In conclusion, LARP4 is proposed to suppress the motility and metastatic potential of ovarian cancer cells.

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