MicroRNAs (miRNA) can regulate cancer cell proliferation and metastasis. Here, we show that miR-338-3p is down-regulated in metastatic tumor tissues compared to primary tumors, and that that miR-338-3p can inhibit cell proliferation by inducing cell cycle arrest, as well as restrain cell migration and invasion. PREX2a is confirmed as a direct target of miR-338-3p. Knockdown of PREX2a inhibits cell proliferation, migration and invasion through the PTEN/Akt pathway. miR-338-3p-dependent inhibition of proliferation and invasion can be rescued by PREXa. Overall, this study demonstrates that miR-338-3p affects the PTEN/Akt pathway by down-regulating PREX2a. This newly identified function of miR-338-3p provides novel insights into neuroblastoma and may foster therapeutic applications.

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Long noncoding RNAs (lncRNAs) are reported to be involved in the pathology of numerous cancers, including neuroblastoma (NB). lncRNA SNHG7 has been recognized as a carcinogen in several cancers, but its role in NB progression remains unknown. Our study revealed that SNHG7 expression was markedly higher in NB tissues than that in nontumor tissues. Besides, upregulated SNHG7 was greatly correlated with poor overall survival of NB patients. Functionally, the loss‐of‐function assays demonstrated that knockdown of SNHG7 inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition in NB cells. Mechanically, the bioinformatics analysis predicted that miR‐653‐5p was the shared partner of SNHG7 and signal transducer and activator of transcription 2 (STAT2). Unsurprisingly, we further confirmed that SNHG7 could interact with miR‐653‐5p and therefore functioned as the ceRNA of STAT2 so as to regulate STAT2 expression in NB cells. Moreover, STAT2 expression was in inverse proportion to miR‐653‐5p level but in positive proportion to SNHG7 level in NB tissues. Importantly, the repressed NB progression induced by silenced SNHG7 was reversed by STAT2 overexpression or miR‐653‐5p inhibitors. Jointly, our findings elucidated SNHG7 facilitated NB progression through the miR‐653‐5p/STAT2 pathway, providing a novel therapeutic target and prognostic biomarker for this disease.

Neuroblastoma is the primary cause of cancer death in childhood. METTL14 is tightly linked to cancer. However, whether single-nucleotide polymorphisms (SNPs) in the METTL14 gene could predispose to neuroblastoma susceptibility lacks evidence. With an epidemiology case-control study, associations between METTL14 gene SNPs and overall risk for neuroblastoma were estimated in 898 cases and 1,734 controls. Following that, stratified analysis was performed. Among the five analyzed SNPs, rs298982 G>A and rs62328061 A>G exhibited a significant association with decreased susceptibility to neuroblastoma, whereas the associations with increased neuroblastoma susceptibility were observed for rs9884978 G>A and rs4834698 T>C. Moreover, subjects carrying two to five risk genotypes were more inclined to develop neuroblastoma than those with zero to one risk genotypes. The stratified analysis further demonstrated the protective effect of rs298982 G>A and rs62328061 A>G, as well as the predisposing effect of rs4834698 T>C and two to five risk genotypes, in certain subgroups. Haplotype analysis was performed. Moreover, false-positive report probability analysis validated the reliability of the significant results. The expression quantitative trait locus analysis revealed that rs298982 is correlated with the expression levels of its surrounding genes. Our results suggest that some SNPs in the METTL14 gene are associated with predisposition to neuroblastoma.

is the most common non-central nerve system (CNS) solid tumor in pediatrics [1]. Neuroblastoma accounts for approximately 8% of all pediatric cancers but disproportionally causes a high cancer mortality (15%) in children [2]. Pediatric patients with low-risk neuroblastoma witness a 5-year overall survival rate > 90%, whereas the 5-year overall survival rate in high-risk neuroblastoma pediatric patients is < 40% [3]. Genetic susceptibility to neuroblastoma is a promising area of research and needs to be fully investigated. For sporadic neuroblastoma, genome-wide association studies (GWASs) have identified over a dozen causal genetic loci. Studies of candidate genes also reported a decent number of variants predisposing to neuroblastoma. However, the known genetic alternations still could not unveil the full genetic underpinnings of neuroblastoma. The base excision repair (BER) pathway, one of the DNA repair systems, is responsible for repairing numerous oxidized and alkylated bases by recognizing and excising damaged bases [4]. Many core proteins are involved in the BER pathway, including poly(ADP)ribose polymerase 1 (PARP1), human 8-oxoguanine DNA glycosylase (OGG1), flap endonuclease 1 (FEN1), apurinic/apyrimidinic endonuclease 1 (APEX1), DNA ligase III (LIG3), and x-ray repair cross-complementing group 1 (XRCC1). OGG1 is a bifunctional enzyme (DNA glycosylase and AP lyase)