miR-143-3p inhibits invasion and migration of gastric cancer by targeting LASP1

  Background  Distant metastasis is a major risk factor affecting the prognosis of gastric cancer (GC) patients and often leads to treatment failure. Therefore, it is urgent to explore new therapeutic targets for tumor metastasis to improve the prognosis of GC patients.

  Objective  To explore whether the miRNAs we screened by bioinformatics analysis could inhibit the invasion and migration of GC cells by targeting LASP1.

  Methods  Based on TCGA database, the expression levels of miRNAs in GC and the correlation between LASP1 and miRNAs were analyzed by bioinformatic methods to predict miRNAs targeting LASP1. The targeted interaction between miR-143-3p and LASP1 was verified by dual-luciferase reporter assay. Using GC cell line MGC-803 as experimental object, miR-143-3p mimic, inhibitor and negative controls were transfected, respectively. Accordingly, the experiments were divided into miR-143-3p mimic negative control (NC) group, miR-143-3p mimic group, miR-143-3p inhibitor NC group and miR-143-3p inhibitor group. Transwell invasion assay and wound healing assay were applied to determine the changes of invasion and migration ability of MGC-803 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the messenger RNA (mRNA) expression level of LASP1 in MGC-803 cells after transfection, and western blot (WB) was used to detect the protein expression level of LASP1 in MGC-803 cells.

  Results  Bioinformatics analysis suggested that miR-143-3p might target LASP1 and the correlation between miR-143-3p and LASP1 was r=-0.284 (P＜0.01). The dual-luciferase reporter assay further confirmed that LASP1 was a direct target gene of miR-143-3p (P＜0.01). Transwell invasion assay and wound healing assay confirmed that miR-143-3p significantly inhibited the invasion and migration ability of gastric cancer MGC-803 cells. The results of qRT-PCR showed that the expression level of LASP1 in miR-143-3p mimic group was lower than that in miR-143-3p mimic NC group (P＜0.01), while the expression level of LASP1 in miR-143-3p inhibitor group had a higher expression level of LASP1 than that of the miR-143-3p inhibitor NC group (P＜0.05). The results of WB showed that protein changes of LASP1 were consistent with that of qRT-PCR.

  Conclusion  miR-143-3p could inhibit the invasion and migration of GC cells by targeting and down-regulating LASP1.