Inhibiting of circ-TLK1 inhibits the progression of glioma through down-regulating PANX1 via targeting miR-17-5p

Liu

2023

Annals of Medicine

Aim Low-grade glioma (LGG), which is the second most frequent adult brain malignancy, severely threatens patients’ health and has a high recurrence rate. Histone H3/H4 chaperone anti-silencing function 1 B ( ASF1B ) has a tight association with the initiation and development of tumours. The expression and regulation mechanism of ASF1B in LGG were discussed. Methods ASF1B expression in LGG patients as well as the association of ASF1B with overall survival and disease-free survival of LGG patients were predicted by GEPIA database. The independent prognostic value of ASF1B in LGG patients was investigated by TCGA database. RT-qPCR, together with western blot was applied for the assessment of ASF1B in LGG cell lines. After ASF1B expression was inhibited, CCK8 and colony formation assays judged cell proliferation. Flow cytometry analysis and TUNEL assay appraised cell cycle as well as apoptosis. Cell migratory and invasive capacities were measured by wound healing as well as Transwell assays. Western blot tested the expression of proliferation-, cycle-, apoptosis-, and metastasis-associated proteins. STRING and GeneMANIA database predicted the relationship between ASF1B and tousled-like kinase 1 ( TLK1) . ChIP assay testified the affinity of ASF1B with TLK1. Subsequently, TLK1 was overexpressed and ASF1B expression interfered, and the functional assays were executed. Results ASF1B was discovered to be increased in LGG tissues and cells and indicates an unfavourable prognosis for LGG patients. ASF1B was not an independent prognostic factor for LGG. ASF1B deficiency obstructed the proliferation, cell cycle as well as metastasis of LGG cells, and induced cell death, which might be realized through the interaction with TLK1 . Conclusion The interaction between ASF1B and TLK1 promoted the malignant progression of LGG. Key messages TLK1 interacts with ASF1B. Interference with ASF1B inhibits the proliferative, invasive and migratory capabilities and induces the cycle arrest, along with the apoptosis of LGG cells. The interaction between ASF1B and TLK1 promotes the malignant progression of LGG.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The interaction between ASF1B and TLK1 promotes the malignant progression of low-grade glioma

Liu

2023

Annals of Medicine

“…In addition, PANX1 was also positively correlated with many frequently tested ICs. Recent studies have suggested that PANX1 may have a wide range of biological effects on cancer development, including the promotion of cell proliferation and tumorigenesis in melanoma, brain tumors, and hepatocellular carcinoma [ 36 , 37 , 38 , 39 ]. It has been reported that PANX1, ABC, CALHM1, VRACs, and MACs can regulate TME via ATP release channel modulation in order to exert therapeutic effects against cancer [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of a Prognostic and Early Diagnosis Model for LUAD Based on Necroptosis Gene Signature and Exploration of Immunotherapy Potential

Wang

Zhou

et al. 2022

Cancers

Necroptosis is a type of programmed necrosis that is different from apoptosis and necrosis. Lung cancer has the highest incidence and mortality worldwide, and lung adenocarcinoma is the most common subtype of lung cancer. However, the role of necroptosis in the occurrence and development of LUAD remains largely unexplored. In this paper, four NRGs and nine NRGs determined by big data analysis were used to effectively predict the risk of early LUAD (AUC = 0.994) and evaluate the prognostic effect on LUAD patients (AUC = 0.826). Meanwhile, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), genomic variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune checkpoint analysis were used to explore the enrichment characteristics and immune research related to the prognostic model. In deep data mining, we were surprised to find that prognostic models also regulate the immune microenvironment, cell cycle, and DNA damage repair mechanisms. Thus, we demonstrated a significant correlation between model evaluation results, ICI treatment, and chemotherapeutic drug sensitivity. The low-risk population has a stronger tumor immune response, and the potential for ICI treatment is greater. People at high risk respond less to immunotherapy but respond well to chemotherapy drugs. In addition, PANX1, a core gene with important value in immune regulation, prognosis assessment, and early diagnosis, has been identified for the first time, which provides a new target for the immunotherapy of LUAD as well as a new theoretical basis for the basic research, clinical diagnosis, and individualized treatment of LUAD.

“…TLK1 is a known kinase that regulates replication, transcription, deoxyribonucleic acid (DNA) repair, chromatin assembly, chromosome segregation and aggravates cell injury in pathological models, including neuronal injury and myocardial ischemia-reperfusion injury. Knockdown of circTLK1 has no effects on the mRNA and protein levels of TLK1, suggesting that circTLK1 does not encode a protein ( Wang et al, 2021 ). It has been indicated that circTLK1 played an important role in the occurrence and progression of cancer.…”

Section: Circular Rnas Expressed In Acute Central Nervous System Inju...mentioning

confidence: 99%

Circular RNA in Acute Central Nervous System Injuries: A New Target for Therapeutic Intervention

Liu

Mao

et al. 2022

Front. Mol. Neurosci.

Acute central nervous system (CNS) injuries, including ischemic stroke, traumatic brain injury (TBI), spinal cord injury (SCI) and subarachnoid hemorrhage (SAH), are the most common cause of death and disability around the world. As a kind of non-coding ribonucleic acids (RNAs) with endogenous and conserve, circular RNAs (circRNAs) have recently attracted great attentions due to their functions in diagnosis and treatment of many diseases. A large number of studies have suggested that circRNAs played an important role in brain development and involved in many neurological disorders, particularly in acute CNS injuries. It has been proposed that regulation of circRNAs could improve cognition function, promote angiogenesis, inhibit apoptosis, suppress inflammation, regulate autophagy and protect blood brain barrier (BBB) in acute CNS injuries via different molecules and pathways including microRNA (miRNA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ph1osphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), Notch1 and ten-eleven translocation (TET). Therefore, circRNAs showed great promise as potential targets in acute CNS injuries. In this article, we present a review highlighting the roles of circRNAs in acute CNS injuries. Hence, on the basis of these properties and effects, circRNAs may be developed as therapeutic agents for acute CNS injury patients.