Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical

Tingting Zhang1, Zhang Li1, Jiao Li2

  • 1Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Molecular Cancer
|April 1, 2025
PubMed

Insights

Small open reading frame (sORF)-encoded microproteins regulate gene expression and are implicated in cancer. This review covers their translation, function, and clinical significance as biomarkers and therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Biology

Background:

  • The human genome contains ~20,000 protein-coding genes, with ongoing research into their functions.
  • Small open reading frames (sORFs) in non-coding RNAs or mRNA 5' leaders can produce microproteins.
  • Microproteins regulate gene expression and are crucial for biological processes.

Purpose of the Study:

  • To review microprotein translation mechanisms and identification.
  • To summarize microprotein dysregulation in cancer and their biological functions.
  • To highlight microproteins' roles in cancer progression and their clinical significance.

Main Methods:

  • Literature review of microprotein research.
  • Analysis of translational mechanisms (cap-dependent/independent).
  • Examination of microprotein identification techniques.

Main Results:

  • Microproteins modulate gene expression at multiple levels.
  • Aberrant microprotein expression is linked to cancer initiation and progression.
  • Microproteins play roles in hallmark cancer events.

Conclusions:

  • Microproteins are critical regulators of gene expression with significant roles in cancer.
  • Microproteins hold potential as diagnostic/prognostic biomarkers.
  • Microproteins represent promising therapeutic targets for cancer treatment.

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