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

• DOI: 10.1002/jcp.29073
• Publication Date: 2019-07-17T11:38:45Z
• Authors: Gyeoung Jin Kang; Mi Kyung Park; Hyun Jung Byun; Hyun Ji Kim; Eun Ji Kim; Lu Yu; Boram Kim; Jae Gal Shim; Ho Lee; Chang Hoon Lee
• Keywords: 0301 basic medicine; Epithelial-Mesenchymal Transition; RNA Splicing; Nuclear Proteins; Triple Negative Breast Neoplasms; Mice, SCID; Cadherins; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Antigens, CD; Cell Movement; Mice, Inbred NOD; Cell Line, Tumor; Animals; Heterografts; Humans; Female; Neoplasm Invasiveness; Cell Adhesion Molecules

AbstractTriple‐negative breast cancer (TNBC) is associated with a high mortality rate, which is related to the insufficient number of appropriate biomarkers and targets. Therefore, there is an urgent need to discover appropriate biomarkers and targets for TNBC.SARNP (Hcc‐1 and CIP29) is highly expressed in several cancers. It binds to UAP56, an RNA helicase component of the TREX complex in messenger RNA (mRNA) splicing and export. However, the role of SARNP in mRNA splicing and export and in the progression of breast cancer, especially of TNBC, remains unknown. Therefore, we examined the role of SARNP in mRNA splicing and export and progression of TNBC.We confirmed that SARNP binds to UAP56 and Aly and that SARNP overexpression enhances mRNA splicing, whereas its knockdown suppressed mRNA export. The SARNP overexpression induced the proliferation of MCF7 cells, whereas its knockdown induced E‐cadherin expression and downregulated vimentin and N‐cadherin expressions in SK‐BR‐3 and MDA‐MB‐231 cells. SARNP downregulates E‐cadherin expression by interaction with pinin. Mice injected with MDA‐MB‐231shSARNP cells exhibited a significant reduction in tumor growth and lung metastasis compared with those injected with MDA‐MB‐231shCon cells in vivo.These findings suggested that SARNP is involved in mRNA splicing and export. SARNP maintains mesenchymal phenotype by escaping from inhibitory interaction with pinin leading to the downregulation of E‐cadherin expression.