Wilms tumor (WT) is a common abdominal tumor that accounts for more than 90% of all malignant renal tumors in children (1–3). The incidence of WT is approximately 1/10,000, and the tumor is known to be highly malignant, to grow fast, and to be prone to metastasis (4–8). In most patients, the first symptom typically involves a palpable abdominal mass. Furthermore, some patients tend to exhibit symptoms such as hematuria, fever, urinary tract infection, varicocele, hypertension or hypotension, and anemia (9–11). Surgical resection combined with postoperative chemotherapy and radiotherapy can significantly improve the 5-year survival rate of WT in children (12–14). However, WT treatment still faces several challenges that need to be overcome to improve the effective rate of treatment, such as multi-drug resistance and the frequency of chemotherapy side effects. In addition, our understanding regarding the pathogenesis and the transformation mechanisms of WT remains insufficient, and there is a lack of corresponding effective targeted therapy (15–18). Therefore, it is urgent to identify specific predictors and therapeutic targets for the prognosis of WT.

In the eukaryotic genome, the proportion of protein-encoding genes is very small because approximately only 1.5% of the DNA in the Homo sapiens genome has the ability to perform this specific function (19). In the process of gene expression, DNA follows the principle of base complementary pairing, and is transcribed under the catalysis of RNA polymerase (20, 21). The transcription products are divided into two types according to their protein-encoding ability. One of these two types is RNA that can encode proteins. In contrast, message RNAs (mRNAs), a type of RNA that cannot encode proteins, are collectively referred to as noncoding RNAs (ncRNAs) (22, 23). At present, noncoding RNAs are mainly classified based on their sequence length, and they are divided into small ncRNAs, which have a sequence length of less than 200 nucleotides, and lncRNAs, which have a sequence length of more than 200 nucleotides (24, 25). LncRNAs are mainly in the form of RNA in epigenetic, transcription, and post-transcriptional regulation of gene expression levels (25–28). Most lncRNAs are also catalyzed and transcribed by RNA polymerase II, but their sequences are not highly conserved, their expression abundance is low, and they display strong specificity in tissues and cells (29–32). The mechanism of action of lncRNAs is also relatively complicated and has been continuously explored in recent years. However, some of the known mechanisms include affecting the transcription of the upstream promoter region of the encoding protein gene and interfering with the expression of downstream genes (33), and inhibiting IIIIA polymerase II or mediating chromatin remodeling and histone modification, thus affecting the expression of downstream genes (34). The transcript forms a complementary double-strand that interferes with mRNA shearing, thus forming different forms of shearing (35) and a complementary double-strand with the transcript of the gene encoding protein, while also generating endogenous siRNA under the action of the Dicer enzyme (36), binding to a specific protein to regulate the activity of the corresponding protein (37), acting as a structural component to form a nucleic acid-protein complex with a protein (38) and as a precursor molecule for small RNAs (miRNAs, piRNAs) (39), and also binding to a specific protein to change the cellular location of the protein (40).

At present, many studies have shown that lncRNAs play an indispensable role in tumor occurrence and progression. Lnc-CCLM is downregulated in cervical cancer tissues and is closely related to the lymphatic metastasis of cervical cancer patients (41). Lnc-GAS6-AS1 is downregulated in lung adenocarcinoma tissue, and it has been related to the patients’ clinicopathological characteristics and survival rates (42). Zhao et al. found that the low expression of lncRNA EMX2OS was associated with the poor prognosis of WT subjects (43). In addition, Zhang et al. showed that lncRNA SOX21-AS1 acts as an oncogenic lncRNA in WT. Knockdown of lncRNA SOX21-AS1 inhibits WT cell proliferation and colony formation, and induces cell cycle arrest by upregulating p57 expression (44). Besides, lncRNA also plays an indispensable role in the occurrence and progression of childhood tumors. Kesherwani et al,. have confirmed the lncRNA expression profile in the pediatric MB subgroups and related molecular pathways and the prognostic significance of lncRNAs and unique lncRNAs associated with each MB subgroup were determined and verified (32591022). They identified important lncRNA DELU2, CASC15, LINC01355 and GAS5 exists in each subgroup, which can further explore the functional analysis of different MB subgroups. In addition, they also found that SOX2, PRKCD, and EZH2 are related to the functional network of each subgroup and may be important drug targets. Smith et al. summarize the abnormally expressed ncRNAs in childhood tumors (45). They found that miRNAs and long non-coding RNAs play a key role in the development of these cancers. In addition, their functional contributions and molecular interactions during tumor formation. Baldini et al,. made an overview. The aim is to briefly summarize the latest findings about the involvement of certain lncRNAs in NB disease by focusing on the mechanism of action of certain lncRNAs involved in NB disease and revealing the possible role in the pathogenesis and progression of NB (45). Liu et al. identified a ceRNA network consisting of 38 DElncRNAs, 18 DEmiRNAs and 99 DEmRNAs was established and 7 prognostic-related RNAs by analyzing the TCGA database (46). It was found through analysis that two RNAs were related to clinical staging and organization. The scientific classification is significantly related, and the 7 RNAs may be considered as new prognostic biomarkers and potential therapeutic targets for WT treatment. In addition, the ceRNA regulatory network can provide new strategies for the further study of lncRNA and miRNA in WT.

This article aims to systematically review the latest research progress of LncRNAs in the field of WT, hoping to provide a theoretical basis for LncRNAs as possible biomarkers and potential therapeutic targets for WT in the future.

At present, the underlying cause of WT is unclear, and may be related to gene mutations that regulate normal embryonic development in the urogenital tract. Studies have shown that lncRNAs are differentially expressed in WT, which can affect tumor proliferation, invasion, metastasis, and other biological effects through transcriptional and post-transcriptional regulation ( Table 1 ). LncRNAs can interact with miRNAs through a competitive endogenous RNA mechanism, influence the expression of downstream genes, and thus affect the overall disease process ( Figure 2 ). LncRNAs can also induce the malignant progression of WT by regulating related pathways ( Figure 3 ). In addition, lncRNAs have the potential to become tumor markers and potential therapeutic targets in WT ( Table 2 ).

The discovery of lncRNAs has filled many gaps regarding the molecular mechanism of biological processes. IncRNA performs the functions of signal, scaffold, decoy, and guide molecules. It has also been found that it regulates gene expression from the three levels of transcription, post-transcription, and epigenetics, and it participates in almost all processes of living organisms. However, considering the huge number of lncRNAs and their significant levels of complexity, well-researched lncRNAs are essentially the tip of the iceberg, and there are still many undiscovered functions of lncRNAs. Of course, with the improvement of the current sequencing level and the advancement of research technology, continuously more and more lncRNAs have been found to play important functions in regulating cell cycle, disease occurrence, stem cell differentiation, and cell reprogramming. However, there are many existing challenges. Although more and more lncRNAs have been identified, there are still no unified naming standards. In general, researchers name lncRNAs according to their function and mode of action. However, the definition of lncRNAs is inaccurate. Firstly, not all lncRNAs have a length that is greater than 200 nt, because some sequences annotated as lncRNA can also be less than 200 nt. There are also issues pertaining to the definition of their coding ability because recent studies have found that some lncRNAs have a short open reading frame, which can encode some small peptides.

There are still many problems that need to be overcome, including the means with which we can facilitate early screening for abnormal expression of tumor-related lncRNAs, and intervening, e.g., using related lncRNAs, to improve tumor treatment. Moreover, there are still few studies on lncRNAs in WT. We believe that through continuous in-depth research, lncRNA is expected to become a new opportunity for tumor diagnosis and treatment, and point out a new direction for tumor precision treatment.

In summary, this article reviews the research progress of lncRNAs in WT. Current progress provides new directions and approaches for revealing the molecular mechanism of lncRNAs in WT, and also indicates novel biomarkers for the diagnosis, treatment, and prognosis evaluation of WT.

Original draft preparation, allocation, revision, supplement and edition, QL. All authors have read and agreed to the published version of the manuscript.

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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