Nejvíce citovaný článek - PubMed ID 34207434
All-Trans Retinoic Acid Fosters the Multifarious U87MG Cell Line as a Model of Glioblastoma
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.
- Klíčová slova
- AC016405.3, ADAMTs9-AS2, AGAP2-AS1, AHIF, ANRIL, CASC2, CASC7, CASC9, CCND2-AS1, CRNDE, DCST1-AS1, DGCR5, DLEU1-AS1, ECONEXIN, FAM66C, GAS5, H19, HMMR-AS1, HOTAIR, HOTAIRM1, HOTTIP, HOXA-AS2, HOXB13-1, HULC, KTN1-AS1, LINC-ROR, LINC00461, LINC00467, LINC00565, LINC00641, LINC01393, LINC01426, LINC01446, LINC01494, LINC01503, LINC01711, LINC02283, MAFG-DT, MALAT1, MATN1-AS1, MDC1-AS, MEG3, MIAT, MIR210HG, MNX1-AS1, NCK1-AS1, NEAT1, PART1, PARTICLE, PCA1, PCAT1, PVT1, RBPMS-AS1, RPSAP52, RUNX1-IT1, SAMMSON, SOX2-OT, TALNEC2, TP73-AS1, TSLC1-AS1, TUG1, TUNAR, TUSC7, UCA1, XIST, ZBED3-AS1, ZEB1-AS1, biomarker, blood, glioblastoma multiforme, glioma, liquid biopsy, lnc-TALC, lncRNA, lncRNA-ATB, noncoding RNA, plasma, serum,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.
- Klíčová slova
- Glioblastoma, Hypoxia, Long-surviving patients, Primocultures, STAT3, Temozolomide,
- MeSH
- dospělí MeSH
- glioblastom metabolismus patologie genetika MeSH
- gliom * metabolismus patologie genetika MeSH
- hypoxie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- myši MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory mozku metabolismus patologie genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- transkripční faktor STAT3 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH
- STAT3 protein, human MeSH Prohlížeč
- transkripční faktor STAT3 * MeSH
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.
