Deciphering the Role of microRNA Mediated Regulation of Coronin 1C in Glioblastoma Development and Metastasis

Abstract

Glioblastoma multiforme (GBM) is a highly heterogenic and malignant brain tumour with a median survival of 15 months. The initial identification of primary glioblastomas is often challenging. Coronin 1C (CORO1C) is a key player in actin rearrangement and cofilin dynamics, as well as enhancing the processes of neurite overgrowth and migration of brain tumour cells. Different bioinformatic databases were accessed to measure CORO1C expression at the mRNA and protein level in normal and malignant brains. CORO1C expression was observed in brain regions which have retained high synaptic plasticity and myelination properties. CORO1C was also expressed mainly within the hippocampus formation, including the Cornu Ammonis (CA) fields: CA1–CA4. Higher expression was also noticed in paediatric GBM in comparison to their adult counterparts. Pediatric cell populations were observed to have an increased log2 expression of CORO1C. Furthermore, 62 miRNAs were found to target the CORO1C gene. Of these, hsa-miR-34a-5p, hsa-miR-512-3p, hsa-miR-136-5p, hsa-miR-206, hsa-miR-128-3p, and hsa-miR-21-5p have shown to act as tumour suppressors or oncomiRs in different neoplasms, including GBM. The elevated expression of CORO1C in high grade metastatic brain malignancies, including GBM, suggests that this protein could have a clinical utility as a biomarker linked to an unfavorable outcome.

Proteomic profiling of the brain from the <i>wobbler</i> mouse model of amyotrophic lateral sclerosis reveals elevated levels of the astrogliosis marker glial fibrillary acidic protein

“…High levels of coronin-3 expression have previously been described to occur in diffuse gliomas. 42 Hence, the microglia cell population appears to be elevated in the wobbler mouse brain agreeing with the concept of reactive gliosis. The formation of glial scars is therefore probably associated with impaired motor neuron functions at the level of the central nervous system.…”

MicroRNA-Dependent Mechanisms Underlying the Function of a β-Amino Carbonyl Compound in Glioblastoma Cells

“…CORO1C acts as an F-actin turnover effector influencing neurite overgrowth and migration of brain tumor cells. 40 An elevated expression of CORO1C in metastatic malignancies, such as GB and colorectal cancer, was previously documented, indicating the potential clinical relevance of this gene as a biomarker associated with an unfavorable prognosis. 41 The negative effects of SHG-8 upon this oncogene supported the findings that SHG-8 exerted negative regulation upon de novo neurone overgrowth and the Wnt pathway, thus limiting the proliferative and migratory abilities of U87MG GB cells.…”

“…To strengthen the hypothesis that SHG-8 negatively regulated the Wnt-pathway, an in vitro RT-qPCR of CORO1C revealed that the gene was significantly downregulated in the presence of the drug. CORO1C acts as an F-actin turnover effector influencing neurite overgrowth and migration of brain tumor cells . An elevated expression of CORO1C in metastatic malignancies, such as GB and colorectal cancer, was previously documented, indicating the potential clinical relevance of this gene as a biomarker associated with an unfavorable prognosis .…”