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Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis

Andrei Marian Niculae1,2, Maria Dobre1, Vlad Herlea3

  • 1Victor Babes National Institute of Pathology, 050096 Bucharest, Romania.

Life (Basel, Switzerland)
|October 27, 2022
PubMed

Insights

The let-7 microRNA family is downregulated in colorectal cancer (CRC), impacting insulin-like growth factor (IGF) axis activity. Specific let-7 miRNAs are linked to KRAS mutations and perineural invasion in CRC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Aberrant insulin-like growth factor (IGF) axis signaling drives colorectal cancer (CRC) development and progression.
  • MicroRNAs (miRNAs) of the let-7 family act as tumor suppressors by targeting genes within the IGF axis.

Purpose of the Study:

  • To investigate miRNA-mRNA interactions between let-7 family miRNAs and IGF signaling pathway genes.
  • To analyze the expression of let-7 miRNAs in colorectal cancer tissues and their association with clinical features.

Main Methods:

  • In silico bioinformatic analysis of miRNA-mRNA interactions.
  • Quantitative analysis of let-7 miRNA expression in colorectal cancer (CRC) and adjacent peritumoral tissues.
  • Correlation analysis with KRAS mutations and perineural invasion.

Main Results:

  • Seven let-7 miRNAs (hsa-let-7a-5p, -7b-5p, -7c-5p, -7d-5p, -7e-5p, -7f-5p, -7g-5p) were significantly downregulated in CRC tissues.
  • miR-let-7e-5p was upregulated in CRC with KRAS codon 12 or 13 mutations.
  • let-7a-5p, -7b-5p, -7c-5p, -7d-5p, and -7i-5p dysregulation was observed in CRC with perineural invasion.

Conclusions:

  • The findings support a link between the IGF axis, let-7 miRNAs, and colorectal cancer.
  • let-7 miRNA expression is associated with specific molecular alterations (KRAS mutations) and invasive phenotypes (perineural invasion) in CRC.
Keywords:
colorectal cancerinsulin-like growth factorlet-7 microRNAsperineural invasion

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