miR-454-3p在结肠癌中的表达及其对结肠癌增殖、侵袭及肝转移能力的影响

Expression of miR-454-3p and its effect on proliferation, invasion and metastasis of colon cancer

目的研究miR-454-3p在结肠癌中的表达及其对结肠癌增殖、侵袭及肝转移能力的影响。方法收集20例结直肠癌患者的肿瘤组织,癌旁组织作为正常对照。应用原位杂交检测结肠癌组织和正常结肠组织中miR-454-3p的表达水平。在结肠癌细胞株SW480中,运用慢病毒转染技术过表达miR-454-3p。应用Cell Counting Kit-8 (CCK-8)和细胞克隆形成实验检测结肠癌细胞增殖能力的变化,Transwell实验检测结肠癌细胞侵袭能力的变化。脾脏注射结肠癌细胞构建小鼠结肠癌肝转移模型,研究过表达miR-454-3p对结肠癌肝转移的影响。结果原位杂交结果显示miR-454-3p在结肠癌组织中的表达水平显著高于正常结肠组织,差异有统计学意义(P<0.05);在人结肠癌细胞SW480中上调miR-454-3p表达能够显著促进肿瘤细胞的增殖和侵袭(P<0.05)。小鼠过表达miR-454-3p组中肝转移结节较对照组显著增多(P<0.05)。结论 miR-454-3p在结直肠癌患者肿瘤组织中表达显著上调,miR-454-3p可能通过促进结肠癌细胞增殖和侵袭进而促进肿瘤的肝脏转移,从而参与了结直肠癌的发展进程。miR-454-3p有望成为结直肠癌诊断和预后评估的一个新的潜在标志物。

Objective To study the expression of miR-454-3p in colon cancer and its effect on colon cancer proliferation, invasion and hepatic metastasis. Methods Specimens of tumor tissues and paired adjacent tissues were collected from 20 patients with colorectal cancer for detecting the expression levels of miR-454-3p using in situ hybridization. Colon cancer cell line SW480 was transfected with a lentiviral vector to induce miR-454-3p over-expression, and the changes in cell proliferation and invasion were observed using cell counting kit-8 (CCK-8), clone formation assay and Transwell experiment. The effect of miR-454-3p over-expression on hepatic metastasis of colon cancer was assessed in BALB/c mouse models. Results The results of in situ hybridization showed a significantly increased expression level of miR-454-3p in colon cancer tissues as compared with normal colon tissues (P<0.05). In SW480 cells, over-expression of miR-454-3p significantly promoted the cell proliferation and invasion (P<0.05). In BALB/c mice, SW480 cells over-expressing miR-454-3p showed a significantly higher potential for liver metastases than the control cells (P<0.05). Conclusion miR-454-3p is overexpressed in the tumor tissues in patients with colorectal cancer and participates in the progression of colorectal cancer by promoting cancer cell proliferation, invasion, and liver metastasis. miR-454-3p may serve as a novel biomarker for colorectal cancer diagnosis and prognostic evaluation.