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Published on: November 2, 2013
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.
Abstract:
The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-coding RNAs or the 5' leader sequences of messenger RNAs, can be translated into small peptides called microproteins through cap-dependent or cap-independent mechanisms. These microproteins interact with diverse molecular partners to modulate gene expression at multiple regulatory levels, thereby playing critical roles in various biological processes. Notably, sORF-encoded microproteins exhibit aberrant expression patterns in cancer and are implicated in tumor initiation and progression, expanding our understanding of cancer biology. In this review, we introduce the translational mechanisms and identification methods of microproteins, summarize their dysregulation in cancer and their biological functions in regulating gene expression, and emphasize their roles in driving hallmark events of cancer. Furthermore, we discuss their clinical significance as diagnostic and prognostic biomarkers, as well as therapeutic targets.
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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