Proteomic screening identifies calreticulin as a miR-27a direct target repressing MHC class I cell surface exposure...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• MicroRNA (miRNA) dysregulation is a hallmark of cancer, influencing immune response and tumour progression.
• Aberrant miRNA expression, alongside genetic and epigenetic changes, contributes to colorectal cancer (CRC) initiation and development.

Purpose of the Study:

• To investigate the role of miR-27a in colorectal cancer (CRC) progression.
• To identify genes and pathways regulated by miR-27a in CRC.
• To explore the therapeutic potential of targeting miR-27a in CRC.

Main Methods:

• Analysis of independent adenoma and CRC miRnoma data sets.
• Differential 2DE-DIGE proteome analysis to identify miR-27a targets.
• In vitro cell culture experiments assessing proliferation and angiogenesis.
• Mouse xenograft models to evaluate tumour growth, apoptosis, and immune cell infiltration.
• In vivo correlation studies of miR-27a with MHC class I, calreticulin, and CD8(+) T cells.

Main Results:

• miR-27a is upregulated in adenoma and further increases during CRC evolution.
• miR-27a targets proteins involved in MHC class I cell surface expression, with calreticulin identified as a direct target.
• miR-27a affects cell proliferation, angiogenesis, and apoptosis in vitro and in vivo.
• In vivo, high miR-27a inversely correlates with MHC class I, calreticulin, and CD8(+) T cell infiltration.
• Tumours with high miR-27a, low calreticulin, and low CD8(+) T cell infiltration exhibit distant metastasis and poor prognosis.

Conclusions:

• miR-27a acts as an oncomiRNA in colorectal cancer (CRC).
• miR-27a represses MHC class I expression via calreticulin downregulation, impacting tumour progression.
• These findings suggest miR-27a as a potential biomarker for diagnosis, patient stratification, and novel therapeutic strategies in CRC.