Silencing of long noncoding RNA MYLK-AS1 suppresses nephroblastoma via down-regulation of CCNE1 through transcription factor TCF7L2

Nephroblastoma, a pediatric kidney cancer, caused by pluripotent embryonic renal precursors. Long noncoding RNAs (lncRNAs) are commonly abnormal expressed in many cancers. In the present study, we fousced on one newly discrovered lncRNA, MYLK Antisense RNA 1 (MYLK-AS1), and its functional role in proliferation and cycle distribution of nephroblastoma cells. Micorarray-based analysis revealed the highly expressed Cyclin E1 (CCNE1) and MYLK-AS1 in nephroblastoma. After nephroblastoma tissue sample collection, RT-qPCR confirmed the upregulated expression of MYLK-AS1 and CCNE1 in nephroblastoma tissues and cells. Kaplan-Meier curve exhibited that patients with elevated CCNE1 had lower overall survival rate in follow-up study. RNA binding protein immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter gene assay were employed to determine the relationship among MYLK-AS1, TCF7L2, and CCNE1, which validated that transcription factor 7-like 2 (TCF7L2) could specifically bind to MYLK-AS1 and TCF7L2 could positively promote CCNE1. After gain- and loss-of function assays, the conclusion that silencing of MYLK-AS1 could inhibit expression of CCNE1 through the transcription factor TCF7L2 to regulate the cell proliferation and cell cycle distribution of nephroblastoma cells was obtained. Subsequently, the subcutaneous tumor formation ability of nephroblastoma cell in nude mice was observed and the silencing of MYLK-AS1 exerts suppressive role in the tumorigenic ability of nephroblastoma cells in vivo. Taken together, MYLK-AS1 constitutes a promising biomarker for the early detection and treatment of nephroblastoma.

Automated summary

Nephroblastoma, a pediatric kidney cancer, is associated with abnormal expression of lncRNA MYLK-AS1, which promotes cell proliferation and cycle distribution through the TCF7L2/CCNE1 signaling pathway. Silencing of MYLK-AS1 inhibits the tumorigenic ability of nephroblastoma cells in vivo, highlighting its potential as a biomarker for early detection and treatment.