Knockdown of lncRNA HAGLROS inhibits metastasis and promotes apoptosis in nephroblastoma cells by inhibition of autophagy

Abstract

Nephroblastoma, or Wilms tumor, is a primary renal malignant tumor that easily occurs in children. Previous studies have revealed the regulatory functions of LncRNA in nephroblastoma. LncRNA HAGLROS functions as a tumor promotor in various cancers including hepatocellular carcinoma, ovarian cancer and colorectal cancer. In this study, the HAGLROS expression in nephroblastoma cells was assayed through qRT-PCR. Cell proliferation assessment employed CCK-8. Moreover, the migration and invasion of cells were examined separately through wound healing and transwell assay. Moreover, flow cytometric analysis and Western blot assay were applied to evaluate cell apoptosis. Rapamycin and 3-methyladenine were used to serve as autophagy activator or inhibitor, respectively. In addition, autophagy was identified by immunofluorescence staining and Western blot analysis. Experiment results showed that HAGLROS expressed highly in nephroblastoma cell lines. HAGLROS knockdown prevented cells from proliferating, and also showed suppressive impact on migration and invasion in HFWT cells. In addition, knockdown of HAGLROS showed a facilitative effect on apoptosis and an inhibitory effect on autophagy. Stimulation of autophagy alleviated HAGLROS silencing-induced apoptosis, while inhibition of autophagy reversed the effect in nephroblastoma cells. In summary, our results revealed that HAGLROS executed an oncogenic role in the progress of nephroblastoma, offering a new perspective on the strategy for nephroblastoma therapy.

Construction and verification of a novel circadian clock related long non-coding RNA model and prediction of treatment for survival prognosis in patients with hepatocellular carcinoma

“…Circadian clock genes work together as a whole to regulate the body's life activities. And LncRNAs play pivotal roles in regulation of circadian clock genes, having different biological functions in various cancer types [ 18 , 19 ]. However, most studies conducted only on a single circadian clock gene, and fewer studies focus on the circadian clock genes as a whole.…”

“…Recent studies have shown that lncRNAs have vital roles in regulation of circadian clock genes. On the other side, LncRNAs play pivotal roles in regulation of circadian clock genes, having different biological functions in various cancer types [ 18 , 19 ]. Ming and colleagues showed that a lncRNA highly expressed in HCC can increase the expression of CLOCK to disrupt the circadian rhythm, resulting in the promotion of HCC [ 20 ].…”

LncRNA OSTM1-AS1 acts as an oncogenic factor in Wilms’ tumor by regulating the miR-514a-3p/MELK axis

“…In the present study, we demonstrated for the first time that OSTM1-AS1 is highly expressed in WT tissues and cell lines. In addition, it has similar effects on WT cells as the lncRNAs MIAT [10], HAGLROS [21] and DGCR8 [22]. In this study, a series of in-vitro and in-vivo experiments demonstrated that OSTM1-AS1 knockdown considerably slowed the malignant development of WT cells.…”

“…In the present study, we demonstrated for the first time that OSTM1-AS1 is highly expressed in WT tissues and cell lines. In addition, it has similar effects on WT cells as the lncRNAs MIAT [10], HAGLROS [21] and DGCR8 [22].…”

The probable role of retroelements in the development of Wilms’ tumor in chromosomal syndromes

“…Например, lncRNA MIAT действует в качестве онкогена за счет регуляторного воздействия на DGCR8 (субъединица комплекса процессинга микроРНК) [60], lncRNA AC007406.1, AC005208.1, LINC01770, DLGAP1-AS2, AP002761.4, STPG3-AS1, AC129507.1, AC234772.2, LINC02447, AC009570.1, ZBTB20-AS1 и LINC01179 вовлечены в патогенез ОВ за счет влияния на ферроптоз [61], HOTAIR [62] и MEG3 [63] -на сигнальные пути Wnt/β-катенина. Нокдаун lncRNA HAGLROS ингибирует метастазы и способствует апоптозу клеток нефробластомы за счет ингибирования аутофагии [64]. Кроме того, lncRNA могут служить эффективными прогностическими биомаркерами ОВ.…”