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

Abstract

Abstract. 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.

MicroRNA‐155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor‐β receptor 2

“…[15][16][17] Previous studies showed that aberrant expression of many miRNAs promote proliferation and metastases in GC. [18][19][20] However, the molecular events are not fully understood.…”

“…Aberrant expression of miRNAs has been found in several cancers, which play novel roles as anti‐oncogenes or oncogenes, depending on the function of the target genes . Previous studies showed that aberrant expression of many miRNAs promote proliferation and metastases in GC . However, the molecular events are not fully understood.…”

MicroRNA‐1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non‐small‐cell lung cancer

“…It has been reported that miR‐1258 can inhibit the migration and metastasis of gastric cancer cells by targeting heparanase . In addition, miR‐1258 can inhibit brain metastases in breast cancer .…”

“…Recent studies have shown that aberrant miRNA expression may play an important role in the development of non‐small‐cell lung cancer . Previous studies have found that miR‐1258 can play its role in the regulation of invasion and metastasis by targeting heparanase in gastric cancer; while in breast cancer, miR‐1258 can also inhibit brain metastasis by degrading heparanase . Furthermore, in NSCLC, a negative correlation between the expression of miR‐1258 and heparanase was found .…”

Sorcin induces gastric cancer cell migration and invasion contributing to STAT3 activation

“…Surgery and chemotherapy are the prime treatment for curing the malignancy [ 8 , 20 ]. According to official statistics, about 50% of GC cases suffer metastases at diagnosis [ 21 ]. The 5-year survival rate is greatly decreased in patients with metastases compared with patients diagnosed early in the progression [ 20 ].…”