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Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
Published on: June 16, 2023
Whole-transcriptome analysis reveals the interactions of mRNAs and ncRNAs to predict and validate ceRNA networks in
KunPeng Zhu1,2, XingKai Wang1,2, Lin Fan1
1Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China.
Abstract:
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.
Insights
This study reveals novel competing RNA networks in osteosarcoma lung metastasis. Understanding these interactions offers new therapeutic targets for this challenging cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Metastatic osteosarcoma (OS) presents poor prognosis and limited treatment options, especially for lung metastasis.
- Non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs) are crucial in tumor progression, but their regulatory networks in OS lung metastasis remain unclear.
Purpose of the Study:
- To comprehensively analyze the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in osteosarcoma lung metastasis.
- To identify and characterize competing endogenous RNA (ceRNA) networks involved in OS lung metastasis.
- To validate key regulatory pathways for potential therapeutic targets.
Main Methods:
- Whole transcriptome sequencing (RNA-seq) on matched primary and lung-metastasis OS tissues.
- Bioinformatic analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis.
- Identification of ceRNA networks using RNAhybrid and TargetScan, followed by experimental validation of selected pathways.
Main Results:
- Distinct expression patterns of lncRNAs, circRNAs, miRNAs, and mRNAs were identified in OS lung metastasis.
- Novel ceRNA networks involving lncRNAs, circRNAs, miRNAs, and mRNAs were constructed.
- Two specific ceRNA pathways, lncRNA PCAT1/miR-370-3p/LRAT and circ_0012586/miR-200b-5p/MFAP5, were validated experimentally.
Conclusions:
- The study elucidates the complex regulatory landscape of ceRNAs in osteosarcoma lung metastasis.
- Identified ceRNA networks and validated pathways provide novel insights into the mechanisms of OS lung metastasis.
- These findings may pave the way for new therapeutic strategies against osteosarcoma lung metastasis.
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