SPARC overexpression alters microRNA expression profiles involved in tumor progression

Abstract

Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth in vitro and in vivo and also alters chemo sensitivity. MicroRNAs are a class of post-transcriptional gene regulators with critical functions in tumor progression. In addition, microRNA (miRNA) expression changes are also involved in chemo-resistance. Herein, we assessed microRNA (miRNA) profiling to identify the functional network and biological pathways altered in SPARC-overexpressed medulloblastoma cells. A total of 27 differentially expressed miRNAs were identified between the control and SPARC-overexpressed samples. Potential messenger RNA (mRNA) targets of the differentially expressed miRNA were identified using Ingenuity Pathway Analysis (IPA). Network-based functional analyses were performed on the available human protein interaction and miRNA-gene association data to highlight versatile miRNAs among the significantly deregulated miRNAs using the IPA, and the biological pathway analysis using the PANTHER web-based tool. We have identified six miRNAs (miR-125b1*, miR-146a-5p, miR-181a-5p, miR-204-5p, miR-219-5p and miR-509-3p) that are associated with SPARC sensitivity by comparison of miRNA expression patterns from the SPARC treated cells with the control cells. Furthermore, pathway enrichment analysis outline that these six microRNAs mainly belong to biological processes related to cancer related signaling pathways. Collectively, these studies have the potential to indicate novel biomarkers for treatment response and can also be applied to develop novel therapeutic treatment for medulloblastoma.