NLRC5 Activates the PI3K/AKT Pathway to Facilitate the Invasion and Metastasis of Lung Adenocarcinoma Cells

Background: Studies have shown that nucleotide-binding oligomerization domain (NOD)-like receptors family CARD domain containing 5 (NLRC5) is involved in promoting the transformation and invasion of malignant cancer cells. However, the effects and mechanism of action of NLRC5 in lung adenocarcinoma have yet to be elucidated. The aim of this study was therefore to investigate the effect of NLRC5 expression on the invasion and metastasis of lung adenocarcinoma (LUAD) cells and its mechanisms.Methods: Tumor and tumor-adjacent normal tissues were acquired from LUAD patients admitted to the affiliated Suqian hospital of Xuzhou medical university from June 2017 to December 2019. A549 and H292 cells were transfected with negative siRNA (siNC) and NLRC5 siRNA (si-NLRC5), respectively. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway agonist 740Y-P was added to cells in the si-NLRC5 group, while cells without any treatment were used as controls. NLRC5 expression was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. In addition, the techniques of cell colony formation, Transwell assay and scratch tests were employed to assess cell viability, invasion, and migration, respectively. The expressions of genes related to epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway was also evaluated by Western blot.Results: NLRC5 expression in LUAD cell lines and tissues was markedly increased compared to normal human bronchial epithelial (HBE) cells and tumor-adjacent normal tissues (p < 0.05). Knockdown of NLRC5 expression significantly reduced cell viability, invasion and migration, as well as reducing EMT processes and inhibiting activation of the PI3K/AKT pathway (p < 0.05). However, treatment with 740Y-P partially reversed the impact of NLRC5 knockdown in LUAD cells (p < 0.05).Conclusion: NLRC5 stimulates the invasion and metastasis of LUAD cells through activating the PI3K/AKT pathway.

Automated summary

This study found that NLRC5 promotes the invasion and metastasis of LUAD cells by activating the PI3K/AKT pathway.