[MicroRNA-33a regulates the invasion of cervical cancer cells via targeting Twist1]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2015 Oct;40(10):1060-7. doi: 10.11817/j.issn.1672-7347.2015.10.002.
[Article in Chinese]

Abstract

Objective: To examine the expression of Twist1 in cervical cancer and to explore its biological function in the progression of cervical cancer.

Methods: The expressions of Twist1 in 32 cervical cancers and matched normal tissues were examined by immunohistochemistry (IHC). Cell invasive ability and the expression of invasion-related genes were determined in RNAi-based Twist1-silencing HeLa cells. The relationship between Twist1 and microRNA-33a (miR-33a) in cervical cancer was studied by Pearson correlation analysis, and the roles of miR-33a in regulation of Twist1 and cell invasiveness were studied.

Results: The positive expression rate of Twist1 was 75.0% (24/32) and 21.9% (7/32) in the cervical cancer and the matched normal tissues, respectively, with significant difference between them (P<0.05). Twist1 shRNA significantly decreased the invasiveness of HeLa cells (P<0.05). Compared with the matched normal tissues, the expression of miR-33a was increased in the cervical cancer tissues, which was negatively correlated with Twist1 (r=-0.661, P<0.05). Overexpression of miR-33a could significantly suppress Twist1 expression as well as cell invasiveness (P<0.05).

Conclusion: Twist1 is critical for the invasiveness of cervical cancer cells; miR-33a, as a tumor suppressor gene, functions as an upstream regulator of Twist1 and is involved in the invasiveness of cervical cancer cell.

目的:研究转录因子Twist1在宫颈癌组织中的表达及其在宫颈癌细胞进展过程中的作用。方法:免疫组织化学检测32对临床宫颈癌组织及正常宫颈组织中Twist1的表达情况,并运用RNA干扰技术沉默宫颈癌HeLa细胞内Twist1 后检测细胞的侵袭能力以及侵袭相关基因表达的变化;采用Pearson相关性检验分析Twist1与microRNA-33a(miR-33a)在宫颈癌组织内的关系,并分析miR-33a对Twist1的调节关系及其对细胞侵袭能力的影响。结果:Twist1在宫颈癌组织和正常宫颈组织中表达的阳性率分别为75.0%(24/32)和21.9%(7/32),二者表达差异具有统计学意义(P<0.05);Twist1 shRNA能显著减低HeLa细胞的体外侵袭能力。宫颈癌组织中miR-33a的表达较正常组织减低(P<0.05),并与Twist1呈负相关(r=−0.661,P<0.05);而宫颈癌细胞内过表达miR-33a可减低Tiwst1的表达(P<0.05),并减弱细胞的体外侵袭能力。结论:Twist1在宫颈癌的侵袭转移过程中发挥着重要的作用,miR-33a为上游调控Twist1的表达及细胞侵袭能力的抑癌基因。.

MeSH terms

  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness*
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Twist-Related Protein 1 / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • MIRN33a microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Small Interfering
  • TWIST1 protein, human
  • Twist-Related Protein 1