Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Published: February 2021
AI Article Synopsis
Article Abstract
Juvenile myelomonocytic leukemia (JMML) treatment primarily relies on hematopoietic stem cell transplantation and results in long-term overall survival of 50-60%, demonstrating a need to develop novel treatments. Dysregulation of the non-coding RNA transcriptome has been demonstrated before in this rare and unique disorder of early childhood. In this study, we investigated the therapeutic potential of targeting overexpressed long non-coding RNAs (lncRNAs) in JMML. Total RNA sequencing of bone marrow and peripheral blood mononuclear cell preparations from 19 untreated JMML patients and three healthy children revealed 185 differentially expressed lncRNA genes (131 up- and 54 downregulated). LNA GapmeRs were designed for 10 overexpressed and validated lncRNAs. Molecular knockdown (≥ 70% compared to mock control) after 24 h of incubation was observed with two or more independent GapmeRs in 6 of them. For three lncRNAs (lnc-THADA-4, lnc-ACOT9-1 and NRIR) knockdown resulted in a significant decrease of cell viability after 72 h of incubation in primary cultures of JMML mononuclear cells, respectively. Importantly, the extent of cellular damage correlated with the expression level of the lncRNA of interest. In conclusion, we demonstrated in primary JMML cell cultures that knockdown of overexpressed lncRNAs such as lnc-THADA-4, lnc-ACOT9-1 and NRIR may be a feasible therapeutic strategy.
Objective: Long non-coding RNA (lncRNA) has been playing an increasingly significant role in neuropathic pain (NP). This study aimed to investigate the clinical significance and mechanism of LncRNA ZNFX1 antisense RNA 1 (ZFAS1) in NP.
Methods: 92 patients with NP and healthy controls were enrolled, and a rat NP model was constructed by chronic constrictive injury (CCI).
The origin of genes from non-coding sequences is a long-term and fundamental biological question. However, how de novo genes originate and integrate into the existing pathways to regulate phenotypic variations is largely unknown. Here, we selected seven genes from 782 de novo genes for functional exploration based on transcriptional and translational evidence.
The long non-coding RNA Growth Arrest-Specific 5 (GAS5) is pivotal in modulating key signaling pathways by functioning as a molecular sponge for microRNAs (miRNAs). GAS5 is notably recognized for its antitumor properties, primarily through its ability to sequester oncogenic miRNAs, thereby influencing critical pathways such as p53, Wnt/β-catenin, and PI3K/Akt, all of which are integral to cell proliferation, apoptosis, and metastasis. The disruption of GAS5-miRNA interactions has been implicated in various malignancies, reinforcing its potential as both a biomarker and a therapeutic target.
Retinoblastoma (RB) is an aggressive form of eye cancer. β-Asarone is a bioactive component isolated from the medicinal plant Acorus tatarinowii Schott and has anticancer effects on various human cancers. However, reports regarding the role of β-Asarone in RB remain limited.
Our previous research identified that lncRNA PVT1 is upregulated in patients with IA. However, the precise functions of PVT1 in IA remain unclear. We compared the levels of PVT1, caspase-3, caspase-1, and NLRP3 in normal and IA patients.
