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

Nan Fang Yi Ke Da Xue Xue Bao. 2018 Dec 30;38(12):1421-1426. doi: 10.12122/j.issn.1673-4254.2018.12.04.
[Article in Chinese]

Abstract

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).

Conclusions: 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.

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。

Keywords: colon cancer; invasion; metastasis; microRNA.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Colon / metabolism
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Disease Progression
  • Humans
  • Liver Neoplasms / secondary*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness

Substances

  • Biomarkers, Tumor
  • MIRN454 microRNA, human
  • MicroRNAs

Grants and funding

国家自然科学基金(81470858);无锡市重点学科胃肠病学(DXK002);无锡市第二人民医院樊代明院士工作站(CYR1705);南京医科大学科技发展基金重点项目(2017NJMUZD110)