Therapeutic targeting of FUBP3 phase separation by GATA2-AS1 inhibits malate-aspartate shuttle and neuroblastoma progression via modulating SUZ12 activity.

Malate-aspartate shuttle (MAS) is essential for maintaining glycolysis and energy metabolism in tumors, while its regulatory mechanisms in neuroblastoma (NB), the commonest extracranial malignancy during childhood, still remain to be elucidated. Herein, by analyzing multi-omics data, GATA binding protein 2 (GATA2) and its antisense RNA 1 (GATA2-AS1) were identified to suppress MAS during NB progression. Mechanistic studies revealed that GATA2 inhibited the transcription of glutamic-oxaloacetic transaminase 2 (GOT2) and malate dehydrogenase 2 (MDH2).

Therapeutic targeting of CNBP phase separation inhibits ribosome biogenesis and neuroblastoma progression via modulating SWI/SNF complex activity.

Background: Neuroblastoma (NB) is the most common extracranial malignancy in childhood; however, the mechanisms underlying its aggressive characteristics still remain elusive.

Methods: Integrative data analysis was performed to reveal tumour-driving transcriptional regulators. Co-immunoprecipitation and mass spectrometry assays were applied for protein interaction studies.

Long-Term Survival of Neuroblastoma Patients Receiving Surgery, Chemotherapy, and Radiotherapy: A Propensity Score Matching Study.

Neuroblastoma is the most common extracranial solid malignancy in children. This study was undertaken to determine the long-term survival of neuroblastoma patients receiving conventional therapeutics (surgery, chemotherapy, and radiotherapy). The neuroblastoma patients examined were registered in the Surveillance, Epidemiology and End Results (SEER) database (1975-2016).

Robot-Assisted versus Trans-Umbilical Multiport Laparoscopic Ureteral Reimplantation for Pediatric Benign Distal Ureteral Stricture: Mid-Term Results at a Single Center.

Objective: Robot-assisted laparoscopic ureteral reimplantation (RALUR) and trans-umbilical multiport laparoscopic ureteral reimplantation (TMLUR) are both minimally invasive procedures for benign distal ureteral stricture (DUS). However, TMLUR has rarely been reported in published research, thus the difference in mid-term outcome of these two procedures warrants investigation. Methods: Patients who underwent RALUR or TMLUR for pediatric DUS from April 2017 to November 2020 at our institution were retrospectively analyzed and 56 patients were included in this retrospective comparison.

Circ-CTNNB1 drives aerobic glycolysis and osteosarcoma progression via m6A modification through interacting with RBM15.

Objectives: Circular RNAs (circRNAs) are a subclass of noncoding RNAs, playing essential roles in tumorigenesis and aggressiveness. Recent studies have revealed the pivotal functions of circ-CTNNB1 (a circular RNA derived from CTNNB1) in cancer progression. However, little is known about the role of circ-CTNNB1 in osteosarcoma (OS), a highly malignant bone tumour in children and adolescents.

HNF4A-AS1-encoded small peptide promotes self-renewal and aggressiveness of neuroblastoma stem cells via eEF1A1-repressed SMAD4 transactivation.

Cancer stem cells play crucial roles in tumorigenesis and aggressiveness, while regulatory mechanisms in neuroblastoma (NB), a pediatric extracranial malignancy with highest incidence, are still unknown. Herein, a small 51-amino acid peptide (sPEP1) encoded by hepatocyte nuclear factor 4 alpha antisense RNA 1 (HNF4A-AS1) was identified in tumor tissues and cells, which facilitated self-renewal and aggressiveness of NB stem cells. MiRNA-409-5p interacted with HNF4A-AS1 to facilitate sPEP1 translation via recruiting eukaryotic translation initiation factor 3 subunit G, while sPEP1 repressed serum deprivation-induced senescence and promoted sphere formation, growth, or metastasis of NB stem cells.

Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression.

Macroautophagy/autophagy is a conserved cellular process associated with tumorigenesis and aggressiveness, while mechanisms regulating expression of autophagic machinery genes in cancers still remain elusive. Herein, we identified E2F4 (E2F transcription factor 4) as a novel transcriptional activator of cytoprotective autophagy crucial for zinc homeostasis in cancer cells. Gain- and loss-of-function studies showed that promoted autophagy in a cell cycle-dependent manner, resulting in facilitated degradation of MT (metallothionein) proteins, elevated distribution of Zn within autophagosomes, decreased labile intracellular zinc ions, and increased growth, invasion, and metastasis of gastric cancer cells.

Therapeutic targeting of SPIB/SPI1-facilitated interplay of cancer cells and neutrophils inhibits aerobic glycolysis and cancer progression.

Background: As a metabolic reprogramming feature, cancer cells derive most of their energy from aerobic glycolysis, while its regulatory mechanisms and therapeutic strategies continue to be illusive.

Methods: Integrative analysis of publically available expression profile datasets was used to identify critical transcriptional regulators and their target glycolytic enzymes. The functions and acting mechanisms of transcriptional regulators in cancer cells were investigated by using in vitro and in vivo assays.

p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation.

Background: Metabolic reprogramming sustains tumorigenesis and aggressiveness of neuroblastoma (NB), the most common extracranial malignancy in childhood, while underlying mechanisms and therapeutic approaches still remain elusive.

Methods: Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP) sequencing, and RNA sequencing assays were applied to explore protein interaction and target genes.

HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression.

Background: Aerobic glycolysis is a hallmark of metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of glycolytic genes in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain elusive.

Methods: Crucial transcriptional regulators and their downstream glycolytic genes were identified by integrative analysis of a publicly available expression profiling dataset.

Therapeutic targeting of YY1/MZF1 axis by MZF1-uPEP inhibits aerobic glycolysis and neuroblastoma progression.

As a hallmark of metabolic reprogramming, aerobic glycolysis contributes to tumorigenesis and aggressiveness. However, the mechanisms and therapeutic strategies regulating aerobic glycolysis in neuroblastoma (NB), one of leading causes of cancer-related death in childhood, still remain elusive. : Transcriptional regulators and their downstream glycolytic genes were identified by a comprehensive screening of publicly available datasets.

Long Noncoding RNA NHEG1 Drives β-Catenin Transactivation and Neuroblastoma Progression through Interacting with DDX5.

Recent studies suggest that long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functional roles and underlying mechanisms of lncRNAs in neuroblastoma (NB), the most common malignant solid tumor in pediatric population, still remain elusive. Herein, through integrating analysis of a public RNA sequencing dataset, neuroblastoma highly expressed 1 (NHEG1) was identified as a risk-associated lncRNA, contributing to an unfavorable outcome of NB.

Circ-HuR suppresses HuR expression and gastric cancer progression by inhibiting CNBP transactivation.

Background: Circular RNAs (circRNAs), a subclass of non-coding RNAs, play essential roles in tumorigenesis and aggressiveness. Our previous study has identified that circAGO2 drives gastric cancer progression through activating human antigen R (HuR), a protein stabilizing AU-rich element-containing mRNAs. However, the functions and underlying mechanisms of circRNAs derived from HuR in gastric cancer progression remain elusive.

Therapeutic targeting of circ-CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression.

Aerobic glycolysis is a hallmark of metabolic reprogramming in tumor progression. However, the mechanisms regulating glycolytic gene expression remain elusive in neuroblastoma (NB), the most common extracranial malignancy in childhood. Herein, we identify that CUT-like homeobox 1 (CUX1) and CUX1-generated circular RNA (circ-CUX1) contribute to aerobic glycolysis and NB progression.

Therapeutic Targeting of /PARP1/E2F1 Axis Inhibits Proline Synthesis and Neuroblastoma Progression.

Proline synthesis plays an important role in the metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of proline synthetic genes in neuroblastoma (NB) remain elusive. Herein, through integrative screening of a public dataset and amino acid profiling analysis, myeloid zinc finger 1 () and antisense RNA 1 () are identified as transcriptional regulators of proline synthesis and NB progression.