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OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial-Mesenchymal

Shuai Guo1, Yang Sun1

  • 1Division of No.2 Gastrointestinal Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.

Cancer Management and Research
|April 14, 2022
PubMed
Abstract

Insights

This study identified the OTOP2/miR-3148 axis as a potential regulator in colorectal cancer (CRC) pathogenesis. Lower OTOP2 expression in CRC tissues correlated with poor survival, and its modulation affected cancer cell progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Colorectal cancer (CRC) is a common malignancy with unclear pathogenesis.
  • Multi-omics data aids in understanding CRC pathophysiology and identifying biomarkers.
  • Gene Expression Omnibus (GEO) datasets offer valuable resources for CRC research.

Purpose of the Study:

  • To identify potential therapeutic targets for colorectal cancer by analyzing GEO datasets.
  • To investigate the role of specific genes and microRNAs in CRC pathogenesis.
  • To elucidate the regulatory mechanism of the OTOP2/miR-3148 axis in colorectal cancer.

Main Methods:

  • Differential gene expression (DEG) analysis of CRC datasets (GSE50760, GSE104178).
  • Functional enrichment analysis (Gene Ontology, KEGG pathways).
  • Construction of protein-protein interaction (PPI) and miRNA-mRNA networks.
  • In vitro assays (qRT-PCR, caspase activity, wound healing, CCK-8, luciferase reporter assays) to validate findings.

Main Results:

  • Fifty-three overlapped genes were identified, with ten hub genes from PPI network analysis.
  • High OTOP2 expression in CRC tissues correlated with better patient survival, contrary to other identified genes.
  • OTOP2 expression was significantly lower in CRC tissues than in normal tissues.
  • OTOP2 knockdown promoted migration, proliferation, and epithelial-mesenchymal transition in CRC cell lines.
  • miR-3148 was found to inversely regulate OTOP2 expression in CRC cells.

Conclusions:

  • The OTOP2/miR-3148 axis plays a significant role in colorectal cancer pathophysiology.
  • OTOP2 may serve as a potential prognostic biomarker for colorectal cancer.
  • Targeting the OTOP2/miR-3148 axis could offer novel therapeutic strategies for CRC.
Keywords:
CRCDEGsOTOP2functional enrichmentmiR-3148survival analysis

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