References Experimental Model Major Findings
Zhang et al.[17]
This study aims to determine the role of ZFAS1 in the regulation of miR-1271-5p/HK2. In vitro model: U251, T98G, A172, LN229 and HS683 glioma cell lines In vivo model: Xenograft nude mice injected with U251 cells transfected with lentivirus vectors containing shZFAS1. Human Glioma tissues (n=59) from Tongling People’s Hospital, China: Grade I (n=11), Grade II (n=22), Grade III (n=17) and Grade IV (n=9) Human glioma samples Grades III and IV have higher expression of ZFAS1 than glioma grade I and II. U251 and T98G cell lines have the highest ZFAS1 expression compared to A172, LN229 and HS683. Si-ZFAS1 of U251 and T98G cell lines decreased cell proliferation, while increasing apoptosis and inhibiting cell invasion. Similarly, silencing of ZFAS1 reduced tumor growth in xenograft nude mice. miR-1271-5p expression which was lower in glioma tissues and glioma cell lines compared to normal brain tissues and NHA, were increased in si-ZFAS1 transfected cells than in si-NC transfected cells. ZFAS1 increased the expression of Hexokinase 2 (HK2) in glioma cells by targeting miR-1271-5p. This is evident where ZFAS1 inhibition suppressed HK2 expression, and the suppressive effect could be eliminated by combining it with a miR-1271-5p inhibitor. ZFAS1 promoted the development of glioma through regulating miR-1271-5p/HK2 axis by acting as the miR-1271-5p sponge to increase HK2 expression.
Li et al.[57]
This study aims to determine the role of ZFAS1 in regulating miR1505p / PLP2. In vitro model: U87, U251, LN229, and T98G cell lines In vivo model: Xenograft model-U87 cells expressing sh‐ZFAS1 were injected into the mice. Human glioma tissues (n=27) from Nanjing First Hospital, China: Grade II (n=7), Grade III (n= 10), Grade IV (n=10) ZFAS1 expression is highest in grade IV gliomas. U87 and U251 cell lines have higher ZFAS1 expression than T98G and LN229 cell lines. Knockdown of ZFAS1 increased the susceptibility of U87 and U251 to temozolomide. miR‐150‐5p expression was lower in glioma tissues than in normal brain tissues and was shown to be negatively correlated to ZFAS1 expression in glioma tissue. ZFAS1 promoted proliferation, migration and invasion and increased resistance to temozolomide in glioma cells by sponging miR‐150‐5p to regulate Proteolipid protein 2 (PLP2). ZFAS1 knockdown reduced PLP2 expression, and the inhibitory effect was partially reversed by miR-150-5p inhibitors. sh-ZFAS1 significantly inhibited tumour growth in xenograft nude mice as evident in the reduction of average volume and weight of the tumours.
Yang et al.[36]
This study aims to determine the regulation of miR-432-5p by ZFAS1. In vitro model: U87, U251, A172 and LN299 glioma cell lines Human glioma tissue (n=25) from Shanxian Central Hospital, China: Lower grade glioma; I and II (n=10), High-grade glioma; III and IV (n=15) U251 and LN229 cells have the highest ZFAS1 expression compared to U87 and A172. High ZFAS1 expression was correlated with advanced tumor stage and shorter overall survival in glioma. miR‐432‐5p expression was down‐regulated in grade III‐IV gliomas compared to grade I‐II gliomas. Similarly, miR‐432‐5p expression was decreased in glioma cell lines. miR‐432‐5p was suggested to be a target of ZFAS1, where silencing of ZFAS1 increases the miR‐432‐5p expression, reduced cell viability, improves cisplatin cytotoxicity while increasing the apoptosis of U251 and LN229 cells. This is further confirmed by the downregulation of miR4325p, which lowered the effects of ZFAS1 knockdown on cisplatin cytotoxicity and cell viability in glioma cells.
Lv et al.[19]
This study aims to elucidate the molecular mechanisms of ZFAS1 in regulating the epithelial– mesenchymal transition (EMT) in glioma cancer. In vitro model: HS683, T98G, U87, and U251 human glioma cell lines Human glioma tissues (n=69) from First Affiliated Hospital of Nanchang University, China: Astrocytomas, n=45; oligodendrogliomas, n=7; ependymomas, n=3; choroid plexus tumours, n=2, and others, n=8 Patients with high ZFAS1 expression exhibited a lower overall survival time than patients with low ZFAS1 expression, suggesting that ZFAS1 overexpression may serve as an independent prognostic marker for glioma patients. ZFAS1 expression level was higher in high grade glioblastoma cell lines (T98G, U87, and U251) compared with the grade glioma cell line (HS683) Si-ZFAS1 suppressed cell proliferation, decreased colony formation, induced apoptosis, impeded cell migration, and cell invasion in U87 and U251 cells. ZFAS-1 silencing increased the G0/G1 phase of the cell cycle while decreasing the S phase. ZFAS1 was proposed to enhance glioma migration and invasion by promoting EMT progression. This is demonstrated by the negative correlation between the level of E-cadherin and ZFAS1 expression, as opposed to other EMT markers, N-cadherin, Integrin β1, ZEB1, and Twist, which are associated with ZFAS1 expression.
Gao et al.[18]
This study aims to determine the regulation of epithelial–mesenchymal transition (EMT) and Notch signaling pathway by ZFAS1. In vitro model: U87 and U251 glioma cell lines Human glioma tissues (n=46) from Affiliated Hospital of Hebei University of Engineering, China. ZFAS1 expression was upregulated in high grade (III–IV) glioma compared to low grade (I–II). ZFAS1 inhibition suppressed the cells proliferation, migration and invasion, and induced apoptosis in U87 and U251 cells. ZFAS1 was found to promote glioma development via the EMT and Notch signalling pathways, where the expression of EMT-related proteins, E-cadherin, was increased and the expression of proteins N-cadherin and Snail was decreased in si-ZFAS1 transfected glioma cells, while Notch signal-related proteins Hes-1 and NICD were decreased.