Low miR-1273a expression predicts poor prognosis of colon cancer and facilitates tumor cell proliferation, migration, and invasion

Abstract

MicroRNAs (miRNAs) have been indicated to be frequently dysregulated in various cancers and promising biomarkers for colon cancer. The present study aimed to assess the prognostic significance and biological function of miR-1273a in colon cancer. The expression levels of miR-1273a was estimated using quantitative real-time polymerase chain reaction. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1273a in patients of colon cancer. The effects of miR-1273a on cell proliferation, migration, and invasion were investigated by cell experiments. The expression of miR-1273a was downregulated in colon cancer tissues and tumor cell lines compared with the normal controls (all P<0.001). The aberrant expression of miR-1273a was associated with vascular invasion (P=0.005), differentiation (P=0.023), lymph node metastasis (P=0.021), and TNM stage (P=0.004). The patients with low miR-1273a expression had low overall survival compared with the patients with high miR-1273a expression (log-rank P=0.002). miR-1273a was detected to be an independent prognostic biomarker for patients. Furthermore, the results of cell experiments revealed that miR-1273a downregulation promoted, while miR-1273a upregulation suppressed the cell proliferation, migration, and invasion. In conclusion, all data indicated that a downregulated expression of miR-1273a predicted poor prognosis for colon cancer and enhanced tumor cell proliferation, migration, and invasion. Thus, we suggest that methods to promote miR-1273a expression may serve as novel therapeutic strategies in colon cancer.

Figure 1. Expression of miR-1273a in colon cancer tissues and cell lines. A, The expression level of miR-1273a was downregulated in colon cancer tissues compared with the adjacent normal controls. B, The expression level of miR-1273a in colon cancer cell lines was lower than in the normal controls. Data are reported as means±SD. ***P<0.001 (Student's t-test or ANOVA followed by Tukey's test). NCM460: normal colonic mucosa cell line.

Figure 2. Kaplan-Meier survival curves for the patients with colon cancer. Overall survival in the patients with low miR-1273a expression was poor compared with the patients with high miR-1273a expression (log-rank P=0.002).

Figure 3. The expression of miR-1273a in (A) LoVo and (B) SW620 cell lines was significantly promoted by miR-1273a mimic, while it was significantly repressed by miR-1273a inhibitor compared with the untreated cells. The proliferation of both (C) LoVo and (D) SW620 cells was significantly promoted by miR-1273a downregulation, whereas it was significantly suppressed by miR-1273a upregulation. Data are reported as means±SD. *P<0.05, ***P<0.001 (ANOVA followed by Tukey's test). NC: negative control.

Figure 4. A and B, The upregulation of miR-1273a suppressed, whereas the downregulation of miR-1273a promoted, the migration of colon cancer cells. C and D, Similarly, the invasion of colon cancer cells was suppressed by miR-1273a upregulation, whereas it was promoted by miR-1273a downregulation. Data are reported as means±SD. **P<0.01 (ANOVA followed by Tukey's test).