MiR-451, a potential prognostic biomarker and tumor suppressor for gastric cancer

Abstract

Background: The expression of microRNA-451 (miR-451) and its association with clinical pathological factors in GC remain still unclear. The purpose of this study was to investigate if miR-451 is a potential prognostic biomarker and tumor suppressor for gastric cancer.

Methods: Real-time quantitative RT-PCR (qRT-PCR) was applied to detect miR-451 expression in GC cell lines and primary tumor and paired non-cancerous tissues. The association of miR-451 expression with clinicopathological factors and prognosis was statistically analyzed.

Results: We found that miR-451 showed decreased expression in GC tissues and cell lines, and its down-regulation tended to be positively correlated with lymphatic metastasis, clinical staging and shorter overall survival of patients. In addition, forced expression of miR-451 in BGC-823 and MKN-45 cells did not impact on cell proliferation, but did reduce migration and invasion rates in BGC-823 cells.

Conclusion: Our findings indicated that miR-451 may act as a novel prognostic marker and potential therapeutic target in human GC.

Keywords: MiR-451; gastric cancer; metastasis; prognosis.

Figure 1

Expression of miR-451 in gastric cancer (GC) tissues and cell lines. The expression levels of miR-451 were determined by qRT-PCR. A. Pairwise comparison of miR-451 expression between GC and matching non-cancerous tissues showing miR-451 expression was reduced in 28% (30/107) of the sample pairs. The expression level of miR-451 was calculated by the 2^-ΔCt method, after normalized to U6 RNA. B. MiR-451 expression was reduced in four human GC cell lines: MKN-45, BGC-823, MKN-28, and SGC-7901 cells, when compared to that in normal gastric GES cells. Data were represented as mean ± SD from three independent experiments (*P < 0.05, **P < 0.01, ***P < 0.001).

Figure 2

Overall survival curves for two groups defined as low and high expression of miR-451 in GC patients. Lower miR-451 expression was significantly associated with poorer outcome of patients (P < 0.05, log-rank test).

Figure 3

Effects of miR-451 over-expression on GC cell proliferation. A. The expression level of miR-451 in miR-451 containing lentivirus infected cells was significantly higher compared with negative control (NC) transfected cells. qRT-PCR was done to detect the expression of miR-451 in three independent experiments. U6 small nuclear RNA was used as the internal control. ***P < 0.001, **P < 0.01. B. Cell proliferation was measured by MTT assays in BGC-823 and MKN-45 cells infected with miR-451 or NC containing lentivirus. The plates were read every one day for 5 consecutive days. Data were represented as mean ± SD from the experiments performed in triplicate.

Figure 4

MiR-451 inhibits GC cell migration and invasion in vitro. Over-expression of miR-451 significantly inhibited abilities of cell migration and invasion in miR-451-expressing stable BGC-823 cells compared with NC group. Data were expressed as the mean ± SD of at least three independent experiments (*P < 0.05). The migration and matrigel invasion assays showed that the number of migrated or invaded cells was significantly lower in the miR-451-overexpressed group than in the NC group (**P < 0.01).