Whole-transcriptome analysis reveals the interactions of mRNAs and ncRNAs to predict and validate ceRNA networks in osteosarcoma with lung metastases

Due to the poor prognosis and lack of effective therapy options, treating metastatic osteosarcoma (OS), particularly lung metastasis, presents significant therapeutic challenges. It has been shown that both non-coding RNAs (ncRNAs) and protein-coding mRNAs serve as essential for controlling the progression of tumors. Uncertainty persists regarding the whole expression profile and the network of regulation involving competing endogenous RNAs (ceRNAs) between mRNAs and ncRNAs in the OS lung metastasis. To fully understand variations in the expression of lncRNAs, circRNAs, miRNAs, and mRNAs, we introduced whole transcriptome sequencing (RNA-seq) in the three matched primary and lung-metastasis OS tissues used in the current study. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) was carried out for mRNAs exhibiting notably distinct expression patterns. After that, the official RNA hybrid and TargetScan databases were utilized to anticipate and establish the ceRNA networks, which are made up of lncRNAs, circRNAs, miRNAs, and mRNAs. Furthermore, two created ceRNA regulatory pathways, lncRNA PCAT1/miR-370-3p/LRAT, and circ_0012586/miR-200b-5p/MFAP5, were chosen at random and verified using a variety of cell and molecular biology experiments. Ultimately, our research may reveal novel avenues for the prevention or treatment of OS lung metastasis as well as fresh evidence for the underlying mechanism.