If Artificial In Vitro Microenvironment Can Influence Tumor Drug Resistance Network via Modulation of lncRNA Expression?—Comparative Analysis of Glioblastoma-Derived Cell Culture Models and Initial Tumors In Vivo

Abstract

The tumor resistance of glioblastoma cells in vivo is thought to be enhanced by their heterogeneity and plasticity, which are extremely difficult to curb in vitro. The external microenvironment shapes the molecular profile of tumor culture models, thus influencing potential therapy response. Our study examines the expression profile of selected lncRNAs involved in tumor resistance network in three different glioblastoma-derived models commonly utilized for testing drug response in vitro. Differential expression analysis revealed significant divergence in lncRNA profile between parental tumors and tumor-derived cell cultures in vitro, including the following particles: MALAT1, CASC2, H19, TUSC7, XIST, RP11-838N2.4, DLX6-AS1, GLIDR, MIR210HG, SOX2-OT. The examined lncRNAs influence the phenomenon of tumor resistance via their downstream target genes through a variety of processes: multi-drug resistance, epithelial–mesenchymal transition, autophagy, cell proliferation and viability, and DNA repair. A comparison of in vivo and in vitro expression identified differences in the levels of potential lncRNA targets, with the highest discrepancies detected for the MDR1, LRP1, BCRP and MRP1 genes. Co-expression analyses confirmed the following interrelations: MALAT1–TYMS, MALAT1–MRP5, H19–ZEB1, CASC2–VIM, CASC2–N-CAD; they additionally suggest the possibility of MALAT1–BCRP, MALAT1–mTOR and TUSC7–PTEN interconnections in glioblastoma. Although our results clearly demonstrate that the artificial ex vivo microenvironment changes the profile of lncRNAs related to tumor resistance, it is difficult to anticipate the final phenotypic effect, since this phenomenon is a complex one that involves a network of molecular interactions underlying a variety of cellular processes.

LINC01268 and CTB-31O20.2 as Prognostic and Functional Protective Immune Related lncRNAs in Glioblastoma

“…An article was illustrated AC064875.2 as potential prognostic biomarker may regulate neutrophil in ltration in glioma [39]. MIR210HG was reported up-regulation upon hypoxia exposure in glioma cells, and was considered a resistance in GBM therapy [40,41]. Transcriptome sequencing and qRT-PCR con rmed that lncRNA SMIM25 was high expression in cerebral cavernous malformations on the before study [42].…”

Immune-related lncRNAs, LINC01268 and CTB-31O20.2, as favorable prognostic markers for glioma inhibition

“…LncRNA AC064875.2 shows potential prognostic biomarker and may regulate neutrophil infiltration in glioma ( 42 ). Similarly, MIR210HG was reported up-regulation upon hypoxia exposure in glioma cells, and was considered a resistance in GBM therapy ( 43 , 44 ). Transcriptome sequencing and qRT-PCR confirmed that lncRNA SMIM25 had high expression in cerebral cavernous malformations ( 45 ).…”

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

“…Namely, the results of the analysis of EMT markers in cell lines derived from tumors of various types indicate that the levels of TYMS mRNA are increased in cell lines with a predominance of the mesenchymal-like phenotype (Siddiqui et al 2017 ). However, some caution should be exercised when comparing the results of lncRNA interaction in cell lines in vitro with respect to the interaction of the complex network of non-coding RNA in metastatic cancer cells (Witusik-Perkowska et al 2022 ).…”