SARNP, a participant in mRNA splicing and export, negatively regulates E-cadherin expression via interaction with...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) presents a high mortality rate due to limited biomarkers and therapeutic targets.
• The role of SARNP (Hcc-1 and CIP29), a protein highly expressed in cancers and involved in mRNA processing, in TNBC progression is largely unknown.
• Understanding SARNP's function in mRNA splicing and export is crucial for developing new TNBC strategies.

Purpose of the Study:

• To investigate the role of SARNP in mRNA splicing and export.
• To determine SARNP's contribution to the progression of triple-negative breast cancer.
• To explore SARNP as a potential therapeutic target for TNBC.

Main Methods:

• Confirmation of SARNP binding to UAP56 and Aly.
• Assessment of mRNA splicing and export upon SARNP overexpression and knockdown.
• Evaluation of cell proliferation, epithelial-mesenchymal transition markers (E-cadherin, vimentin, N-cadherin), and in vivo tumor growth and metastasis in mouse models.
• Investigation of SARNP's interaction with pinin in regulating E-cadherin expression.

Main Results:

• SARNP overexpression enhanced mRNA splicing, while its knockdown suppressed mRNA export.
• SARNP overexpression increased MCF7 cell proliferation; knockdown induced E-cadherin and downregulated vimentin/N-cadherin in other cell lines.
• SARNP downregulates E-cadherin via interaction with pinin.
• In vivo studies showed reduced tumor growth and lung metastasis in mice injected with SARNP-knockdown MDA-MB-231 cells.

Conclusions:

• SARNP plays a significant role in mRNA splicing and export.
• SARNP promotes TNBC progression by maintaining the mesenchymal phenotype through E-cadherin downregulation.
• SARNP represents a promising therapeutic target for triple-negative breast cancer.