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MiR-1587 Regulates DNA Damage Repair and the Radiosensitivity of CRC Cells via Targeting LIG4

Ruixue Liu1,2, Liping Shen2, Chuxian Lin2

  • 1Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, People's Republic of China.

Dose-Response : a Publication of International Hormesis Society
|July 9, 2020
PubMed

Insights

MicroRNA-1587 (miR-1587) enhances colorectal cancer radiosensitivity by inhibiting DNA Ligase 4 (LIG4) expression, leading to increased DNA damage and cell cycle arrest. This suggests miR-1587 is a potential therapeutic target for colorectal cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • DNA double-strand breaks (DSBs) are critical lesions impacting DNA replication and cell survival.
  • Cancer cell DNA repair capacity influences radiosensitivity, but the role of specific microRNAs, like miR-1587, in radiation resistance remains unclear.
  • Colorectal cancer (CRC) presents a significant health challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of miR-1587 in regulating the growth and radiosensitivity of colorectal cancer (CRC) cells.
  • To determine if miR-1587 affects DNA Ligase 4 (LIG4) expression and its impact on DNA repair.
  • To explore the potential of miR-1587 as a therapeutic target for enhancing CRC radiosensitivity.

Main Methods:

  • Overexpression of miR-1587 in CRC cell lines.
  • Assessment of cell growth, apoptosis, and cell cycle progression.
  • Measurement of DNA double-strand breaks (DSBs).
  • Analysis of DNA Ligase 4 (LIG4) mRNA and protein levels.
  • Dual-luciferase reporter assays to confirm direct binding of miR-1587 to the LIG4 3'-untranslated region.

Main Results:

  • Overexpression of miR-1587 inhibited CRC cell growth and promoted apoptosis.
  • miR-1587 overexpression led to increased DSBs and cell cycle arrest.
  • miR-1587 significantly repressed both LIG4 mRNA and protein expression.
  • Dual-luciferase assays confirmed direct binding of miR-1587 to the LIG4 3'-UTR.
  • miR-1587 mimics enhanced the radiosensitivity of CRC cells.

Conclusions:

  • miR-1587 overexpression enhances DNA damage, arrests cell growth, and increases radiosensitivity in colorectal cancer cells.
  • These effects are mediated through the direct repression of LIG4 expression.
  • miR-1587 plays a novel role in DNA damage repair and radiosensitivity in CRC.
  • miR-1587 represents a promising therapeutic target for colorectal cancer treatment.
Keywords:
DNA double-strand breaksLIG4miR-1587radiosensitivity

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