miR-4757-3p Inhibited the Migration and Invasion of Lung Cancer Cell via Targeting Wnt Signaling Pathway

Abstract

Lung cancer accounts for the vast majority of cancer-related deaths worldwide, and aberrant miRNA expression is commonly observed as the disease progresses. The current study aimed to determine the role of miR-4757-3p in the development of lung cancer. The real-time PCR test was performed to determine the expression of miR-4757-3p in lung cancer cell lines. miR-4757-3p was downregulated in A549 cells. CCK8 and transwell assays demonstrated that overexpression of miR-4757-3p significantly reduced A549 cell invasion and migration. Bioinformatic analysis by the TargetScan database predicted the possible targets of miR-4757-3p. A luciferase activity test was used to determine the direct relationship between miR-4757-3p, Wnt5a, and Wnt8b. The overexpression of miR-4757-3p drastically inhibited the expression of Wnt5a and Wnt8b. Furthermore, we discovered that silencing Wnt5a and Wnt8b significantly lowered β-catenin expression and hampered invasion and migration. Finally, miR-4757-3p inhibited lung cancer cell migration and invasion by inhibiting the activation of the Wnt signaling pathway. Our study provided evidence that miR-4757-3p could be developed as an indicator or an anticancer target in the clinical application.

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

“…Numerous negative regulators increase the transcriptional or protein level of multiple Wnt ligands, including WNT1 [ 153 – 155 ], WNT2B [ 156 ], WNT3A [ 157 – 159 ], WNT5A [ 160 , 161 ], WNT5B [ 162 ] and WNT8B [ 160 ] (Table 3 ). WNT1 expression was increased by miR-383 [ 153 ], miR-924 [ 155 ] and TMEM100 [ 154 ] (Table 3 ), whose expression was significantly decreased in NSCLC tissues and cells.…”

“…WNT3A expression was negatively regulated by circCCT3 [ 157 ], GPC5 [ 158 ] and GRIK3 [ 159 ] (Table 3 ). The expression of WNT5A and WNT8B was increased by miR-4757-3p in NSCLC cell lines [ 160 ]. The long isoform of WNT5A was targeted by miR-1253, which inhibited the proliferation and metastasis of NSCLC cells [ 161 ].…”