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circPTEN suppresses colorectal cancer progression through regulating PTEN/AKT pathway

Chen Li1,2, Xu Li1

  • 1Department of Pathology, the First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an City 710061, Shaanxi Province, China.

Molecular Therapy. Nucleic Acids
|December 23, 2021
PubMed

Insights

Circular RNAs (circRNAs) like circPTEN are crucial in colorectal cancer (CRC). This study shows circPTEN suppresses CRC progression by regulating the PTEN/AKT pathway, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) play significant roles in human malignancies, including colorectal cancer (CRC).
  • The tumor suppressor gene Phosphatase and tensin homolog (PTEN) is critical in cancer, but its derived circRNAs are understudied.
  • Limited research exists on the function of circRNAs originating from the PTEN gene in cancer development.

Purpose of the Study:

  • To investigate the role and mechanism of a specific circRNA derived from PTEN, termed hsa_circ_0094343 (circPTEN), in colorectal cancer (CRC).
  • To determine if circPTEN expression levels correlate with CRC progression and to elucidate its functional impact on CRC cells.
  • To explore the molecular pathways through which circPTEN exerts its effects in CRC, focusing on PTEN/AKT signaling.

Main Methods:

  • Quantitative real-time PCR was used to assess circPTEN expression in CRC tissues and cell lines.
  • Functional assays including cell proliferation, migration, invasion, and apoptosis assays were performed to evaluate circPTEN's impact.
  • Mechanism assays involved investigating the interaction between circPTEN, microRNA-4470 (miR-4470), PTEN, AKT, and TRAF6.
  • Rescue assays were conducted using insulin-like growth factor 1 (IGF-1) and PTEN knockdown to validate circPTEN's function.

Main Results:

  • circPTEN exhibited low expression in CRC tissues and cells compared to normal controls.
  • Upregulation of circPTEN significantly inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis.
  • Mechanistically, circPTEN increased PTEN expression by sequestering miR-4470 and inhibited AKT phosphorylation by interfering with TRAF6-mediated K63-linked ubiquitination.
  • Rescue experiments confirmed that circPTEN's suppressive effects on CRC were reversed by IGF-1 or PTEN knockdown.

Conclusions:

  • circPTEN acts as a tumor suppressor in colorectal cancer.
  • circPTEN inhibits CRC progression by upregulating PTEN and consequently suppressing the PTEN/AKT signaling pathway.
  • circPTEN represents a potential diagnostic biomarker and therapeutic target for colorectal cancer.
Keywords:
AKTTRAF6circPTENcolorectal cancermiR-4470

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