Association of MicroRNA-652 Expression with Radiation Response of Colorectal Cancer: A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy

Curr Gene Ther. 2023;23(5):356-367. doi: 10.2174/1566523223666230418111613.

Abstract

Background: Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified microRNA-652 (miR-652) value on radiotherapy response and outcome in rectal cancer patients.

Methods: miR-652 expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of miR-652 with biological factors and the prognosis was examined. The biological function of miR-652 was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53+/+ and p53-/-) were used for in vitro study. The molecular interactions of miR-652 and tumor suppressor genes were studied through a computational approach.

Results: In RT patients, miR-652 expression was significantly decreased in cancers when compared to non-radiotherapy cases (P = 0.002). High miR-652 expression in non-RT patients was with increased apoptosis marker (P = 0.036), ATM (P = 0.010), and DNp73 expression (P = 0.009). High miR-652 expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation (P = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of miR-652 with apoptosis in rectal cancer. miR-652 expression in cancers was negatively related to WRAP53 expression (P = 0.022). After miR-652 inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53+/+ cells was significantly increased compared with HCT116 p53-/- cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable.

Conclusion: Our findings suggest the potential value of miR-652 expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.

Keywords: TCGA; apoptosis; miR-652; preoperative radiotherapy; prognosis; rectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Humans
  • MicroRNAs* / genetics
  • Molecular Docking Simulation
  • Prognosis
  • Rectal Neoplasms* / genetics
  • Rectal Neoplasms* / pathology
  • Rectal Neoplasms* / radiotherapy
  • Sweden
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Tumor Suppressor Protein p53
  • Biomarkers, Tumor
  • MicroRNAs
  • MIRN652 microRNA, human