Abstract:
Objective To investigate the effect and mechanism of importin5 (IPO5) gene expression on esophageal cancer (EC) progression.
Methods The data and surgical specimens of 50 patients diagnosed with EC in The First Affiliated Hospital of Jinzhou Medical University from September 2020 to April 2022 were collected. The expression of IPO5 in cancer tissues and adjacent tissues was determined using immunohistochemistry. The correlation between IPO5 expression and patient clinical information was evaluated. Lentivirus transfection was used to generate an IPO5-silenced EC cell model. Cell proliferation, invasion, and migration were measured using CCK-8, Transwell invasion, and cell scratch assays. Flow cytometry and Western blot were used to detect cell cycle-related and RAS pathway-related proteins. A subcutaneous tumorigenesis nude mouse model was established, and Ki-67 expression was determined using immunohistochemistry.
Results In clinical samples, IPO5 expression was significantly higher in cancer tissues than that in adjacent tissues (P<0.01) and was positively correlated with tumor size, stage, and degree of differentiation (P<0.05). EC cells expressed higher IPO5 levels than normal esophageal cells, especially ECA109 and OE33 cells (P<0.01). The proliferation and invasion abilities of the IPO5 gene silencing group were decreased (P<0.05 and P<0.01, respectively) compared with that of the negative control group. After IPO5 silencing, the EC cells were arrested in the G2 phase of the cell cycle, and the expression of cell cycle-related proteins decreased. The level of activated RAS-ERK pathway proteins decreased after sh-IPO5 knockdown (P<0.05). Tumorigenesis experiments in nude mice confirmed that tumor shrank ( P <0.05) and Ki-67 expression decreased (P<0.01) after IPO5 gene silending.
Conclusions IPO5 is highly expressed in EC tissues, and inhibition of IPO5 has a significant inhibitory effect on the growth and migration of EC cells. IPO5 activates the RAS-ERK signaling pathway and promotes EC development.