Expression of the circulating and the tissue microRNAs after surgery, chemotherapy, and radiotherapy in mice mammary tumor

Tumour Biol. 2016 Oct;37(10):14225-14234. doi: 10.1007/s13277-016-5292-7. Epub 2016 Aug 26.

Abstract

The expression of microRNAs (miRNAs), as novel biomarkers, is subject to change in many cancers. Therefore, the overall profile of miRNAs can be used for detection of cancer type, response to therapies, pathological variables, and other factors related to the disease. In this study, to evaluate miRNA expression associated with the tumor progression and response to treatment, 60 BALB/c mice received subcutaneous injections of 4T1 cells. The study includes ten groups: one group as control, six groups were euthanized at different time points to assess the role of miRNA expression in the tumor progression, and three groups received chemotherapy, radiotherapy, and surgery to evaluate miRNA expression in response to treatment. MicroRNAs were extracted from the breast tumor and the plasma samples, and their relative expressions were quantified using qRT-PCR. MiR-155 expression was increased in the plasma in the early weeks after the cell injection but decreased in the plasma after surgery and radiotherapy and also in tumor samples after chemotherapy and radiotherapy. MiR-10b expression was increased in the late weeks both in the plasma and the tumor and was decreased in the plasma after radiotherapy and surgery and in the tumor after radiotherapy. MiR-21 expression was increased in the plasma and the tumor tissue during the disease progression at the third and the fourth weeks following tumor induction but was decreased in the plasma in all the therapy groups. Interestingly, miR-125a showed a significant decrease during the tumor progression, and its expression was increased after the treatment. Our results showed that the candidate miRNAs could be divided into two groups of oncomiRs and tumor suppressor miR based on their deregulation after tumor growth and treatments. It seems that the oncomiRs in the plasma can be an ideal noninvasive candidate biomarker for the early detection of breast cancer and also for following the response of the common therapies.

Keywords: Breast cancer; Chemotherapy; Mice; MicroRNA; Radiotherapy; Surgery.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Body Weight
  • Cell Proliferation
  • Combined Modality Therapy
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Mammary Neoplasms, Animal / genetics*
  • Mammary Neoplasms, Animal / pathology
  • Mammary Neoplasms, Animal / therapy
  • Mastectomy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplastic Cells, Circulating / pathology*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • Radiotherapy*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Burden
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Messenger