Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood.

Glioblastoma multiforme (GBM) is a primary brain cancer of poor prognosis, with existing treatments remaining essentially palliative. Current GBM therapy fails due to rapid reappearance of the heterogeneous neoplasm, with models suggesting that the recurrent growth is from treatment-resistant glioblastoma stem-like cells (GSCs). Whether GSCs depend on survival/proliferative cues from their surrounding microenvironmental niche, particularly surrounding the leading edge after treatment remains unknown. Simulating human GBM in the laboratory relies on representative cell lines and xenograft models for translational medicine. Due to U87MG source discrepancy and differential proliferation responses to retinoic acid treatment, this study highlights the challenges faced by laboratory scientists working with this representative GBM cell line. Investigating the response to all trans-retinoic acid (ATRA) revealed its sequestering of the prominin-1 stem cell marker. ICAM-1 universally present throughout U87MG was enhanced by ATRA, of interest for chemotherapy targeting studies. ATRA triggered diverse expression patterns of long non-coding RNAs PARTICLE and GAS5 in the leading edge and established monolayer growth zone microenvironment. Karyotyping confirmed the female origin of U87MG sourced from Europe. Passaging U87MG revealed the presence of chromosomal anomalies reflective of structural genomic alterations in this glioblastoma cell line. All evidence considered, this study exposes further phenotypic nuances of U87MG which may belie researchers seeking data contributing towards the elusive cure for GBM.

The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study’s objectives were to address this preclinical issue and assess prominin-1, ICAM-1, PARTICLE and GAS5 as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear PARTICLE expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. GAS5 identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA PARTICLE into the context of human GBM pathogenesis while substantiating the role of GAS5 as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer.

Objectives: To describe longitudinal changes in functional performance, movement quality, respiratory function, and exploratory biological changes during intensive rehabilitation based on neuroproprioceptive “facilitation and inhibition” principles in a child with spinal muscular atrophy (SMA). Methods: This case report describes a girl with SMA type II receiving disease-modifying therapy, including gene therapy, who completed three intensive rehabilitation programs based on neuroproprioceptive “facilitation and inhibition” principles, alternating equine-assisted and individualized outpatient physiotherapy. Clinical, biomechanical, respiratory, and functional outcomes were assessed before and after each therapeutic block. Exploratory molecular analyses were performed only during the second and third programs. International Classification of Functioning, Disability and Health (ICF)-based documentation and home video recordings were obtained before each rehabilitation program and 28 days after completion. Results: Following rehabilitation, improvements were observed in cervical muscle endurance, gross motor function, upper-limb movement quality, spontaneous motor activity, and functional independence. After two rehabilitation blocks, the child successfully performed expiratory maneuvers yielding numerical spirometric results, although the absence of baseline values precluded quantification of changes in respiratory function. The Expanded Hammersmith Functional Motor Scale score increased from 48 to 54 points. The primary outcome, the standard Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score, remained at its maximum of 64/64 throughout. This persistent ceiling effect precluded detection of further changes using the standard score. Three-dimensional motion analysis documented changes consistent with movement goals defined from the pre-intervention clinical assessment, particularly after Equine-Assisted Physiotherapy based on Neuroproprioceptive “Facilitation and Inhibition” (NEUROEQUIP-SMA). Exploratory analysis of peripheral blood long non-coding RNA (lncRNA) expression showed variable temporal changes across the rehabilitation periods, the biological significance of which cannot be determined from a single participant. Conclusions: This case illustrates continued motor development and changes in movement quality during intensive rehabilitation following gene therapy in a child with SMA type II. The contribution of physiotherapy cannot be separated from ongoing development and pharmacological treatment effects and warrants further investigation.