Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, 603203, Tamil Nadu, India.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec;397(12):9475-9502. doi: 10.1007/s00210-024-03265-7. Epub 2024 Jul 15.
Glioblastoma (GBM) is an aggressive type IV brain tumor that originates from astrocytes and has a poor prognosis. Despite intensive research, survival rates have not significantly improved. Noncoding RNAs (ncRNAs) are emerging as critical regulators of carcinogenesis, progression, and increased treatment resistance in GBM cells. They influence angiogenesis, migration, epithelial-to-mesenchymal transition, and invasion in GBM cells. ncRNAs, such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are commonly dysregulated in GBM. miRNAs, such as miR-21, miR-133a, and miR-27a-3p, are oncogenes that increase cell proliferation, metastasis, and migration by targeting TGFBR1 and BTG2. In contrast, lncRNAs, such as HOXD-AS2 and LINC00511, are oncogenes that increase the migration, invasion, and proliferation of cells. CircRNAs, such as circ0001730, circENTPD7, and circFOXO3, are oncogenes responsible for cell growth, angiogenesis, and viability. Developing novel therapeutic strategies targeting ncRNAs, cell migration, and angiogenesis is a promising approach for GBM. By targeting these dysregulated ncRNAs, we can potentially restore a healthy balance in gene expression and influence disease progression. ncRNAs abound within GBM, demonstrating significant roles in governing the growth and behavior of these tumors. They may also be useful as biomarkers or targets for therapy. The use of morpholino oligonucleotides (MOs) suppressing the oncogene expression of HOTAIR, BCYRN1, and cyrano, antisense oligonucleotides (ASOs) suppressing the expression of ncRNAs such as MALAT1 and miR-10b, locked nucleic acids (LNAs) suppressing miR-21, and peptide nucleic acids (PNAs) suppressing the expression of miR-155 inhibited the PI3K pathway, tumor growth, angiogenesis, proliferation, migration, and invasion. Targeting oncogenic ncRNAs with RNA-interfering strategies such as MOs, ASOs, LNAs, CRISPR-Cas9 gene editing, and PNA approaches may represent a promising therapeutic strategy for GBM. This review emphasizes the critical role of ncRNAs in GBM pathogenesis, as well as the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.
胶质母细胞瘤（GBM）是一种源自星形胶质细胞的侵袭性 IV 级脑肿瘤，预后较差。尽管进行了深入研究，但生存率并未显著提高。非编码 RNA（ncRNA）作为致癌作用、进展和 GBM 细胞治疗耐药性增加的关键调节剂而出现。它们影响 GBM 细胞中的血管生成、迁移、上皮-间充质转化和侵袭。ncRNA，如长 ncRNA（lncRNA）、microRNA（miRNA）和环状 RNA（circRNA），在 GBM 中通常失调。miRNA，如 miR-21、miR-133a 和 miR-27a-3p，是通过靶向 TGFBR1 和 BTG2 增加细胞增殖、转移和迁移的致癌基因。相比之下，lncRNA，如 HOXD-AS2 和 LINC00511，是增加细胞迁移、侵袭和增殖的致癌基因。circRNA，如 circ0001730、circENTPD7 和 circFOXO3，是负责细胞生长、血管生成和活力的致癌基因。针对 ncRNA、细胞迁移和血管生成开发新的治疗策略是治疗 GBM 的一种有前途的方法。通过针对这些失调的 ncRNA，我们有可能在基因表达中恢复健康的平衡，并影响疾病的进展。ncRNA 在 GBM 中大量存在，在调节这些肿瘤的生长和行为方面具有重要作用。它们也可能作为生物标志物或治疗靶点有用。使用抑制 HOTAIR、BCYRN1 和 cyrano 的致癌基因表达的 morpholino 寡核苷酸（MO）、抑制 MALAT1 和 miR-10b 等 ncRNA 表达的反义寡核苷酸（ASO）、抑制 miR-21 的锁定核酸（LNA）和抑制 miR-155 表达的肽核酸（PNA）抑制了 PI3K 通路、肿瘤生长、血管生成、增殖、迁移和侵袭。使用 RNA 干扰策略（如 MO、ASO、LNA、CRISPR-Cas9 基因编辑和 PNA 方法）靶向致癌性 ncRNA 可能代表治疗 GBM 的一种有前途的治疗策略。本综述强调了 ncRNA 在 GBM 发病机制中的关键作用，以及针对这些途径的新治疗策略改善 GBM 患者预后和生活质量的潜力。
