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.
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.
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.
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.
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Published online: July 21, 2022
Accepted: July 7, 2022
Received in revised form: June 24, 2022
Received: September 2, 2021
© 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
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- Commentary on: Long noncoding RNA DLEU2 regulates the progression of Wilm's tumor via miR-539-3p/HOXB2 axisJournal of Pediatric UrologyVol. 19Issue 1
- PreviewYong et al. methodically evaluated the role of the long noncoding RNA (lncRNA) DLEU2/miR-529-3p/HOXB2 axis in Wilm's tumor pathogenesis . Through a set of nicely designed experimental studies, the investigators examined the expression of the novel lncRNA DLEU2 in primary Wilm's tumor tissue, Wilm's tumor cell lines, and a xenograft model, and evaluated its regulation by the microRNA miR-539-3p and involvement in expression of the oncogene HOXB2. While previously found to have relevance in other malignancies, this is the first comprehensive evaluation of the expression of these nucleotides with Wilm's tumor progression.