Long noncoding RNA DLEU2 regulates the progression of Wilm's tumor via miR-539-3p/HOXB2 axis.

J Pediatr Urol

Department of Urology, Hunan Children's Hospital, The Paediatric Academy of University of South China Changsha, Hunan, 410007, PR China.

Published: February 2023

AI Article Synopsis

  • Wilm's tumor is a common kidney cancer in children, and the study focuses on the role of DLEU2, a long noncoding RNA, in its progression.
  • The research utilized various assays to explore how DLEU2 affects cancer cell behaviors like proliferation and invasion, revealing that silencing DLEU2 led to reduced tumor cell activity and increased cell death.
  • Results showed that DLEU2 positively regulates HOXB2 by inhibiting miR-539-3p, suggesting a mechanism that promotes Wilm's tumor malignancy and indicating potential therapeutic targets.

Article Abstract

Background: Wilm's tumor is the most common renal cancer in the pediatric age group. Long noncoding RNAs (lncRNAs) are a kind of RNA transcripts longer than ∼200 nucleotides, which have been revealed to be involved in the progression of Wilm's tumor.

Objective: The purpose of this study was to investigate the function and molecular mechanism of deleted in lymphocytic leukemia 2 (DLEU2) lncRNA in Wilm's tumor progression.

Study Design: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of DLEU2, miR-539-3p and HOXB2 mRNA in Wilm's tumor tissues and cells. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, transwell assay, and flow cytometry were applied to explore the function of DLEU2 in Wilm's tumor cell malignant phenotypes and the regulatory mechanism among DLEU2, miR-539-3p and HOXB2 in Wilm's tumor cells. Western blot examined the protein levels of Bax, Bcl-2 and HOXB2. The relationship between miR-539-3p and DLEU2 or HOXB2 was verified by dual-luciferase reporter assay. Xenograft models of Wilm's tumor were established to study the role of DLEU2 in vivo.

Results: DLEU2 and HOXB2 were significantly highly expressed in primary Wilm's tumor tissues and in vitro cell lines. Silencing of DLEU2 reduced the proliferation, migration and invasion of Wilm's tumor cells, and promoted cell apoptosis. MiR-539-3p was confirmed to be a target of DLEU2. DLEU2 silencing inhibited the malignant behaviors of Wilm's tumor cells by releasing miR-539-3p. In addition, HOXB2 was a target of miR-539-3p. Overexpression of HOXB2 partially restored the inhibitory effects of miR-539-3p on Wilm's tumor cell malignant behaviors. Animal experiments also confirmed the anti-tumor effects of DLEU2 silencing in vivo.

Conclusion: DLEU2 up-regulates the expression of HOXB2 by targetedly repressing miR-539-3p, thereby at least partially promoting the development of Wilm's tumor, these findings provided novel therapeutic targets for Wilm's tumor.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2022.07.010DOI Listing

Publication Analysis

Top Keywords

wilm's tumor
52
wilm's
14
dleu2
13
tumor
13
tumor cells
12
long noncoding
8
mir-539-3p
8
dleu2 mir-539-3p
8
hoxb2
8
mir-539-3p hoxb2
8

Similar Publications

Dipeptidase 1 (DPEP1), initially identified as a renal membrane enzyme in mature human kidneys, plays a pivotal role in various cellular processes. It facilitates the exchange of materials and signal transduction across cell membranes, contributing significantly to dipeptide hydrolysis, glucose and lipid metabolism, immune inflammation, and ferroptosis, among other cellular functions. Extensive research has delineated the complex role of DPEP1 in oncogenesis and tumor progression, with its influence being context dependent.

View Article and Find Full Text PDF

Background: Wilms tumor is one of the most common pediatric kidney cancers with poor prognosis. This study aims to explore the predictive values of lymph nodes (LNs), positive lymph node density (LND) and log odds of positive lymph nodes (LODDS) for the 5-year mortality of children with Wilms tumor.

Methods: The cohort study collected the data of 874 participants with Wilms tumor in the Surveillance, Epidemiology, and End Results (SEER) database.

View Article and Find Full Text PDF

Background: In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.

View Article and Find Full Text PDF

Background: Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015.

Methods: Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls.

View Article and Find Full Text PDF

Background: N6-methyladenosine (m6A) is one of the most conserved internal RNA modifications, which has been implicated in many biological processes, such as apoptosis and proliferation. Wilms tumor 1-associating protein (WTAP), as a key component of m6A methylation, is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Rheumatoid arthritis (RA), a systemic, infiltrating autoimmune disease, is characterized by synovial hyperplasia.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!