miR‑7/SP1/TP53BP1 axis may play a pivotal role in NSCLC radiosensitivity

Oncol Rep. 2020 Dec;44(6):2678-2690. doi: 10.3892/or.2020.7824. Epub 2020 Oct 23.

Abstract

MicroRNA‑7 (miR‑7) has been identified as a tumor suppressor in non‑small cell lung cancer (NSCLC) and a radiosensitivity regulator. Numerous studies have revealed that specific protein 1 (SP1) plays a critical role in the tumorigenesis of various types of cancers and regulates radiosensitivity and tumor suppressor p53‑binding protein 1 (TP53BP1), which plays an essential role in DNA repair. However, it is not clear whether miR‑7 has a regulatory effect on SP1 and TP53BP1 in NSCLC. In the present study it was revealed that miR‑7 directly binds to the 3'UTR of SP1, thereby suppressing SP1 expression to regulate radiosensitivity. Overexpression of miR‑7 and SP1 and knockdown of miR‑7 and SP1 were performed using lentiviral transfection. Protein and mRNA abundance of SP1 and TP53BP1 were determined using western blotting and RT‑qPCR, respectively, while miR‑7 binding to SP1 was validated using a luciferase reporter assay. Biological function analysis indicated that miR‑7 negatively regulated SP1 and inhibited cell proliferation, migration, and invasion when combined with radiation. It was also revealed that the expression of TP53BP1 was positively regulated by SP1 or negatively regulated by miR‑7. In conclusion, SP1 was a target of miR‑7, and the decreased expression of SP1 resulting from miR‑7 overexpression in NSCLC was vital for improving radiosensitivity in NSCLC cells. Moreover, SP1 expression was detected in 95 paired NSCLC and adjacent normal tissues, and it was determined that SP1 was significantly upregulated in NSCLC tissues and that its upregulation was correlated with the degree of tissue differentiation. Thus, SP1 and/or miR‑7 may be potential molecular targets in NSCLC radiotherapy.

Keywords: specific protein 1; microRNA‑7; radiosensitivity; non‑small cell lung cancer.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / radiation effects
  • Cell Proliferation / genetics
  • Cell Proliferation / radiation effects
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / prevention & control
  • Pneumonectomy
  • Radiation Tolerance / genetics*
  • Radiotherapy, Adjuvant
  • Sp1 Transcription Factor / genetics*
  • Sp1 Transcription Factor / metabolism
  • Tumor Suppressor p53-Binding Protein 1 / genetics
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • MIRN7 microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • SP1 protein, human
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1