FAM201A encodes small protein NBASP to inhibit neuroblastoma progression via inactivating MAPK pathway mediated by FABP5

Abstract

Increasing evidence indicates that long non-coding RNA (lncRNA) is one of the most important RNA regulators in the pathogenesis of neuroblastoma (NB). Here, we found that FAM201A was low expressed in NB and a variety of gain and loss of function studies elucidated the anti-tumor effects of FAM201A on the regulation of proliferation, migration and invasion of NB cells. Intriguingly, we identified the ability of FAM201A to encode the tumor-suppressing protein, NBASP, which interacted with FABP5 and negatively regulated its expression. In vivo assays also revealed NBASP repressed NB growth via inactivating MAPK pathway mediated by FABP5. In conclusion, our findings demonstrated that NBASP encoded by FAM201A played a tumor-suppressor role in NB carcinogenesis via down-regulating FABP5 to inactivate the MAPK pathway. These results extended our understanding of the relationship of lncRNA-encoded functional peptides and plasticity of tumor progression.

Long Non-Coding RNAs in Neuroblastoma: Pathogenesis, Biomarkers and Therapeutic Targets

“…The lncRNA 201 family member A ( FAM201A ) was recently shown to encode a small peptide, NBASP, that suppresses the proliferation, migration, and invasion of neuroblastoma cells [ 54 ]. Immunoprecipitation identified fatty acid-binding protein 5 (FABP5) as an interaction partner of NBASP that had previously been already shown to be upregulated in MYCN-amplified neuroblastoma [ 54 ].…”

“…The lncRNA 201 family member A ( FAM201A ) was recently shown to encode a small peptide, NBASP, that suppresses the proliferation, migration, and invasion of neuroblastoma cells [ 54 ]. Immunoprecipitation identified fatty acid-binding protein 5 (FABP5) as an interaction partner of NBASP that had previously been already shown to be upregulated in MYCN-amplified neuroblastoma [ 54 ]. Through RNA sequencing and lipid metabolomics studies in cell lines overexpressing NBASP, followed by Western blot analyses (for ERK pathway), the authors could show that NBASP inhibits MAPK signaling [ 54 ].…”

“…Immunoprecipitation identified fatty acid-binding protein 5 (FABP5) as an interaction partner of NBASP that had previously been already shown to be upregulated in MYCN-amplified neuroblastoma [ 54 ]. Through RNA sequencing and lipid metabolomics studies in cell lines overexpressing NBASP, followed by Western blot analyses (for ERK pathway), the authors could show that NBASP inhibits MAPK signaling [ 54 ]. This suggests that NBASP peptide delivery might be a therapeutic option to be explored.…”