When cells fail to properly differentiate, a malignant tumor such as RMS develops (20). The head and neck, genitourinary system, and extremities are all possible sites of RMS development (21), despite the disease's relative rarity in comparison to other cancers. Early identification and treatment can significantly improve the dismal prognosis of RMS, hence it is crucial to learn about the disease's unique biomarkers.
In present study, we found important miRNAs and target genes participated in RMS development and metastasis. We use integrated bioinformatics analysis to find hub miRNAs and target genes regulation. Then, evaluated the molecular functions, signaling pathways and miRNAs interactions. This data observed Toll like receptor, cell cycle, cellular aging, PI3K/AKT and oxidative stress. One of the interesting results obtained in this study is the role of target gene miRNAs in the signaling pathway of retinal pigment cells (hsa-miR- 410). This result can also show us the risk of retinoblastoma cancer. Retinoblastoma cancer also originates from the retina, and RMS can choose this tissue to invade other organs of the body. Both RMS and retinoblastoma are considered childhood cancers. So the role of predicted molecules in these pathways can show the importance of these data for us along with other investigated signal pathways.
The miR-410, family of microRNAs is a part of the miR-379/410 miRNA cluster, which plays important roles in many different biological processes and malignant malignancies (22, 23). some studies showed that miR-410 is upregulated in NSCLC cells such A549 and H1299 as well as in NSCLC tissue samples. By directly targeting SLC34A2 or Gsk3 and activating the Wnt/-catenin pathway, overexpression of miR-410 was also found to increase cell proliferation, metastasis, stemness, and chemoresistance. In the past, we show that miR-410 plays a crucial role in tumorigenesis and NSCLC development, acting as an oncogene. Additionally, phosphorylated Akt levels were observed to be elevated in NSCLC when miR-410 was present (24). Surprisingly, wild-type EGFR conferred radiation resistance to A549 and H1299 cells, which allowed them to serve as radioresistant cell lines (25, 26). It is possible that EMT, which promotes metastasis and chemoresistance in NSCLC, is caused by the stabilization or overexpression of Slug as a result of inhibition of Gsk3 or activation of the -catenin pathway (27). Also, radioresistance and EMT are linked with cancer stem cells (CSCs) and Akt phosphorylation. Evidence is growing that miR-410 has a role in promoting EMT and radioresistance in NSCLC (28, 29). High death rates from melanoma persist despite great progress in treatment. Resistance to BRAF inhibitors is facilitated by microRNAs, which regulate gene expression post-transcriptionally. The levels of miR-410-3p were found to be lower than expected in melanoma samples. Vemurafenib stimulates its expression in melanoma cells. Increased miR-410-3p levels conferred resistance to vemurafenib in melanoma cells, while its suppression reduced this resistance. The expression of miR-410-3p was elevated by the introduction of ER stress. AXL expression was found to be increased by miR-410-3p in vitro, and this upregulation associated with invasive phenotypic markers in starBase. The research reveals an unexplored method of melanoma resistance. Vemurafenib causes melanoma cells to produce miR-410-3p through ER stress. It promotes the acquisition of an invasive phenotype, which is responsible for the response to and resistance to BRAF inhibition (30). Zhu et al, found that miR-410-3p expression was significantly reduced in the cancerous tissues. This group found that patients with reduced miR-410-3p expression had a larger proportion of positive lymph node status, as well as inferior 5-year disease-free survival and 5-year overall survival. Nasopharyngeal cancer tissues had significantly lower levels of miR-34c expression than their matched normal counterparts. Normal tissue survival was suppressed when miR-34c was up-regulated, but normal tissue migration was unaffected. Reduced levels of miR-34c were associated with increased survival and migration in matched normal tissues. Patients with nasopharyngeal cancer have biomarkers that predict their overall survival, including miR-410-3p and miR-34c expression. Patients with nasopharyngeal cancer have an independent predictive biomarker in the expression of miR-410-3p and miR-34c, which are molecular markers of early metastasis (31).
Mir-127 is an intriguing short non-coding RNA molecule due to its overlapping gene structure. Lung development, placental formation, and apoptosis are just a few of the processes that miR-127 controls via modulating gene expression. Several types of malignancy have been connected to miR-127 expression that is outside of normal ranges. miR-127 expression is highest at the end of the fetal development process. Overexpressing miR-127 in a foetal lung organ culture system caused improper development, as evidenced by a reduction in terminal bud counts and variations in bud diameters. Hepatocellular carcinoma is associated with miR-127 inhibition. A shift in BCL6 protein, which is a miR-127 target, established the molecular relationship (32). Clinical data from TCGA showed that hsa-mir-127 expression was much higher in glioma cells than in normal tissues or control cells. Low REPIN1 expression and high hsa-mir-127 expression were also associated with shorter survival times. Overexpression of hsa-mir-127 also markedly enhanced glioma cell proliferation, suppressed apoptosis, and boosted invasiveness and motility. Antisense inhibitor of hsa-mir-127 was shown to have the opposite of its intended effect. Notably, hsa-mir-127 overexpression suppressed REPIN1 expression, and a luciferase reporter experiment demonstrated that hsa-anti-tumorigenic mir-127's activity depends in part on its direct targeting of REPIN1. Finally, the hsa-mir-127/REPIN1 pathway appears to have a role in gliomas and hence may provide a viable therapeutic target (33). Melanoma cells were shown to have an increase in FOXD3-AS1 expression, as demonstrated by Wan et al. Loss-of-function tests confirmed that FOXD3-AS1 knockdown in melanoma cells increased apoptosis and decreased cell proliferation and migration. The expression of miR-127-3p was adversely regulated by FOXD3-AS1 in melanoma, and mechanistic studies confirmed this effect. Additionally, miR-127-3p overexpression inhibited melanoma development. The expression of FJX1 was shown to be negatively regulated by miR-127-3p, and miR-127-3p was shown to be capable of combining with FJX1 in melanoma cells. According to rescue tests, overexpression of FJX1 counteracted the effect of FOXD3-AS1 suppression on melanoma development (34). Increased LGMN protein expression is achieved because circLGMN functions as a sponge for miR-127-3p, blocking miR-127-ability 3p's to degrade LGMN mRNA. Mimicking miR-127-3p inhibited the growth and invasion of circLGMN-overexpressing GBM cells. Moreover, overexpression of miR-127-3p suppressed the effect of circLGMN overexpression on GBM malignancy in vivo. Considered as a whole, circLGMN is a new tumor-promoting circRNA that promotes LGMN overexpression by sponging miR-127-3p (35). High levels of miR-127-3p and low levels of DPP10-AS1 and ADCY1 were detected in CCSCs. A correlation was found between low DPP10-AS1 expression and tumour grade, lymph node metastasis, and TNM stage. DPP10-AS1 upregulation suppressed miR-127-3p expression, which in turn boosted ADCY1 protein expression, decreased the protein expression of CCSC-related components, and reduced HT-29 and SW480 cell sphere formation, colony formation, proliferation, invasion, and migration. Additionally, in vivo testing corroborated the aforementioned in vitro results (36).