Long noncoding RNA SNHG14 promotes�the�aggressiveness of retinoblastoma by sponging microRNA‑124 and thereby upregulating STAT3

Abstract

A long noncoding RNA called small nucleolar RNA host gene 14 (SNHG14) has been validated as a key regulator of cellular processes in multiple types of human cancer. However, to the best of our knowledge, the expression status and specific roles of SNHG14 in retinoblastoma (RB) have not been studied. The aims of the present study were to determine the expression status of SNHG14 in RB, assess the effects of SNHG14 on malignant characteristics of RB cells and investigate the mechanisms of action of SNHG14 in RB. SNHG14 expression levels in RB tissue samples and cell lines were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPcR). cell proliferation, apoptosis, migration and invasion in vitro, and tumor growth in vivo were quantitated by the cell counting Kit-8 assay, flow cytometry, migration and invasion assays, and mouse tumor xenograft experiments, respectively. The target microRNA (miRNA) of SNHG14 was predicted by bioinformatics analysis and was subsequently validated by a luciferase reporter assay, RNA immunoprecipitation (RIP) assay, RT-qPcR, and western blot analysis. SNHG14 was identified to be significantly overexpressed in RB tissues and cell lines. SNHG14 overexpression was markedly associated with the intraocular international retinoblastoma classification stage, optic nerve invasion, and differentiation grade among patients with RB. The patients in the SNHG14 high-expression group exhibited shorter overall survival compared with the SNHG14 low-expression group. Functional analysis revealed that SNHG14 silencing inhibited cell proliferation, migration and invasion, and increased apoptosis in vitro, and decreased tumor growth in vivo. SNHG14 directly interacted with, and functioned as a competing endogenous RNA (ceRNA) of, miR-124, consequently upregulating signal transducer and activator of transcription 3 (STAT3). miR-124 inhibition and STAT3 expression recovery attenuated the effects of the SNHG14 silencing on RB cells. In conclusion, SNHG14 served as a ceRNA to upregulate STAT3 by sponging miR-124. Therefore, targeting the SNHG14/miR-124/STAT3 pathway may be an effective therapeutic strategy against RB.

Knockdown of SNHG14 Alleviates MPP+-Induced Injury in the Cell Model of Parkinson’s Disease by Targeting the miR-214-3p/KLF4 Axis

“…Recent studies indicated that SNHG14 functioned as a tumor promoter by sponging different miRNAs in a series of cancers, such as retinoblastoma, pancreatic ductal adenocarcinoma, and osteosarcoma (Hou and Mao, 2020;Sun et al, 2020;Xie et al, 2020). SNHG14 was uncovered to be highly expressed in ischemic stroke, and the inhibition of SNHG14 mitigated neuron inflammatory damage (Qi et al, 2017;Zhong et al, 2019).…”

Long Noncoding RNA TRPM2-AS Promotes the Growth, Migration, and Invasion of Retinoblastoma via miR-497/WEE1 Axis

“…SNHG14 overexpression was involved in the malignant progress in RB patients. And, patients with higher expression of SNHG14 exhibited shorter overall survival than those with lower expression of SNHG14 (Sun et al, 2020). Decreasing SNHG14 inhibited RB cell proliferation, migration, and invasion, promoted apoptosis in vitro, and suppressed tumor growth in mouse tumor xenograft models (Sun et al, 2020).…”

Knockdown of lncRNA SNHG14 alleviates LPS-induced inflammation and apoptosis of PC12 cells by regulating miR-181b-5p

“…Moreover, the expression levels of certain lncRNAs, such as SNHG5 and tectonic family member 2, have been discovered to be upregulated in SCI ( 25 , 26 ). Therefore, therapies that target lncRNAs may hold promise for the treatment of SCI ( 27 ). SNHG14 is located within the Prader-Willi critical region and extends into the region of the ubiquitin protein ligase E3A gene, whose deficiency in brain cells in children was revealed to contribute to neurogenetic disorders ( 28 ).…”