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Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis

Qian Chen1, Qingchun Deng2, Yinglian Pan3

  • 1Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan 430033, China.

Journal of Cancer
|January 6, 2023
PubMed

Insights

This study reveals that elevated miR-653 promotes colorectal cancer (CRC) progression by targeting KLF6. The circSETD3/miR-653/KLF6 pathway offers a potential therapeutic target for colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) remains a significant health challenge with complex molecular underpinnings.
  • Non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), play crucial roles in cancer development.
  • Understanding the specific roles of these molecules is vital for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of miR-653 and circSETD3 in colorectal cancer (CRC).
  • To elucidate the molecular mechanism by which these non-coding RNAs influence CRC progression.
  • To identify potential therapeutic targets within the identified molecular axis.

Main Methods:

  • Analysis of miR-653 expression in CRC tissues and cells.
  • Assessment of the correlation between miR-653 levels and patient prognosis.
  • In vitro experiments to evaluate the effects of miR-653 and circSETD3 on CRC cell proliferation, migration, invasion, and apoptosis.
  • Investigation of the interaction between circSETD3 and miR-653 (sponging activity).
  • Identification of miR-653 targets, specifically KLF6.
  • Evaluation of the impact of hypoxia on miR-653 expression and CRC cell behavior.

Main Results:

  • miR-653 was significantly upregulated in CRC tissues and cells, correlating with poor prognosis.
  • Overexpression of miR-653 promoted CRC cell proliferation, migration, and invasion while suppressing apoptosis.
  • circSETD3 acted as a sponge for miR-653, negatively regulating its function.
  • miR-653 promoted CRC via targeting KLF6; circSETD3 knockdown reversed KLF6 overexpression effects.
  • Hypoxia increased miR-653 expression, enhancing CRC cell proliferation, migration, and invasion.

Conclusions:

  • The circSETD3/miR-653/KLF6 axis plays a critical role in colorectal cancer progression.
  • miR-653 acts as a carcinoma-promoting gene in CRC, influenced by hypoxia.
  • This axis represents a promising therapeutic target for colorectal cancer patients.
Keywords:
CircSETD3Colorectal cancerKLF6MiRNA-653TCGA

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