Summary
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
Graphical AbstractGraphical abstract of how DLEU2/miR-539-3p/HOXB2 axis promotes the progression of Wilm's
tumor.
Keywords
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References
- The genetic changes of Wilms tumour.Nat Rev Nephrol. 2019; 15: 240-251
- Advances in Wilms tumor treatment and biology: progress through international collaboration.J Clin Oncol. 2015; 33: 2999-3007
- Origins of DNA methylation defects in Wilms tumors.Cancer Lett. 2019; 457: 119-128
- Wilms' tumor: biology, diagnosis and treatment.Transl Pediatr. 2014; 3: 12-24
- Long noncoding RNAs and human disease.Trends Cell Biol. 2011; 21: 354-361
- Long non-coding RNAs involved in autophagy regulation.Cell Death Dis. 2017; 8e3073
- LncRNA CRNDE promotes the development of Wilms' tumor by regulating microRNA-424.Eur Rev Med Pharmacol Sci. 2020; 24: 1088-1097
- LncRNA SNHG6 promotes Wilms' tumor progression through regulating miR-429/FRS2 Axis.Cancer Biother Radiopharm, 2021
- LncRNA DLEU2 accelerates the tumorigenesis and invasion of non-small cell lung cancer by sponging miR-30a-5p.J Cell Mol Med. 2020; 24: 441-450
- Knockdown of LncRNA DLEU2 inhibits cervical cancer progression via targeting miR-128-3p.OncoTargets Ther. 2020; 13: 10173-10184
- LncRNA DLEU2 aggravates the progression of hepatocellular carcinoma through binding to EZH2.Biomed Pharmacother. 2019; 118109272
- Comprehensive analysis of lncRNA-mediated ceRNA crosstalk and identification of prognostic biomarkers in Wilms' tumor.BioMed Res Int. 2020; 20204951692
- The widespread regulation of microRNA biogenesis, function and decay.Nat Rev Genet. 2010; 11: 597-610
- Disruption of microRNA nuclear transport in human cancer.Semin Cancer Biol. 2014; 27: 46-51
- Long noncoding RNA SNHG16 acts as an oncogene in Wilms' tumor through sponging miR-200a-3p.Eur Rev Med Pharmacol Sci. 2020; 24: 4145-4151
- MiR-22-3p regulates the proliferation and invasion of Wilms' tumor cells by targeting AKT3.Eur Rev Med Pharmacol Sci. 2020; 24: 5996-6004
- MiR-539-3p promotes the progression of epithelial ovarian cancer by targeting SPARCL1.Eur Rev Med Pharmacol Sci. 2019; 23: 2366-2373
- The anti-tumor effect of miR-539-3p on colon cancer via regulating cell viability, motility, and nude mouse tumorigenicity with CDK14 inhibition.J Gastrointest Oncol. 2020; 11: 899-910
- miR-539-3P inhibits proliferation and invasion of gastric cancer cells by targeting CTBP1.Int J Clin Exp Pathol. 2019; 12: 1618-1625
- Quantification of miRNA-mRNA interactions.PLoS One. 2012; 7e30766
- miR1395p Enhances cisplatin sensitivity in nonsmall cell lung cancer cells by inhibiting cell proliferation and promoting apoptosis via the targeting of Homeobox protein HoxB2.Mol Med Rep. 2021; : 23
- MiR-202-5p suppressed cell proliferation, migration and invasion in ovarian cancer via regulating HOXB2.Eur Rev Med Pharmacol Sci. 2020; 24: 2256-2263
- miR-4324 functions as a tumor suppressor in colorectal cancer by targeting HOXB2.J Int Med Res. 2020; 48300060519883731
- HOXB2 and FOXC1 synergistically drive the progression of Wilms tumor.Exp Mol Pathol. 2020; 115104469
- lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p.Cancer Cell Int. 2021; 21: 376
- LncRNA DLEU2 promotes cervical cancer cell proliferation by regulating cell cycle and NOTCH pathway.Exp Cell Res. 2021; 402112551
- Circ_0004104 accelerates the progression of gastric cancer by regulating the miR-539-3p/RNF2 Axis.Dig Dis Sci. 2021; 66: 4290-4301
- lncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis.Aging (Albany NY). 2019; 11: 7386-7401
Article info
Publication history
Published online: July 21, 2022
Accepted:
July 7,
2022
Received in revised form:
June 24,
2022
Received:
September 2,
2021
Identification
Copyright
© 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
ScienceDirect
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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 [1]. 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.
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