MicroRNA-1258: An invasion and metastasis regulator that targets heparanase in gastric cancer.

Numerous microRNAs (miRNAs/miRs) are involved in suppressing or promoting the formation of cancer. However, to the best of our knowledge, the role of miRNA-1258 in gastric cancer (GC) has not previously been investigated. Our previous study demonstrated an increased expression of heparanase (HPSE) in GC tissues and HPSE-facilitated invasion and metastasis of GC cells. Consequently, in the present study, the function of miR-1258 in the invasion and metastasis of GC cells was investigated to determine whether miR-1258 is associated with GC through HPSE. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine miR-1258 expression in GC cell lines and tissues. A Transwell cell invasion assay and an MTT proliferation assay were used to investigate the effects of miR-1258 on the invasion and proliferation of one of the cell lines, SGC-7901 cells, in vitro. The effect of miR-1258 on SGC-7901 cell metastasis was investigated using an in vivo tumor metastasis formation assay. Western blot analysis and RT-qPCR were used to investigate whether HPSE was a target of miR-1258 in GC. The expression of miR-1258 was significantly downregulated in 3 GC cell lines and 116 GC tissues compared with controls (all P<0.001). An association was identified between decreased miR-1258 expression level and increased age (P=0.042), advanced pathological tumor stage (P=0.027) and positive lymphatic vessel invasion (P=0.044) in patients with GC. Furthermore, the upregulation of miR-1258 expression suppressed SGC-7901 cell invasion in vitro (P<0.001) and inhibited SGC-7901 cell metastasis in vivo (P=0.016). The western blot analysis and RT-qPCR results indicated that miR-1258 downregulated the expression of HPSE at the translational level. The results of the present study indicate that miR-1258 acts as a tumor suppressor to inhibit invasion and metastasis by targeting HPSE. Therefore, miR-1258 may serve as a novel biomarker and therapeutic target in the treatment of GC.