Background:
Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC.
Materials and Methods:
Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription–polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules’ expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues.
Results:
QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes.
Conclusion:
Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.
Background. Long noncoding RNAs (lncRNAs) perform as competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) lead to the advancement of cancer. In this work, we attempted to identify possible long noncoding RNA biomarkers as well as a new regulatory axis in colorectal cancer. This investigation was carried out in consideration of the critical oncogenic function played by miR-616-3p in many malignancies, as well as its regulatory involvement in several signaling pathways.Material and Methods: Differentially expressed lncRNAs (DELs) were identified from Gene Expression Omnibus (GEO) database. Targeted mRNAs were recognized by the Targetscan database. ciBioPortal database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis also were applied to identify mRNAs. CeRNA networks constructed via Cytoscape 3.7.1. QRT-PCR was utilized to verify these RNA molecules' expression levels in 30 CRC tissues compared to 30 adjacent tissue samples. Results: Three lncRNAs and three mRNAs were discovered to have the greatest interaction with miR-616-3p. QRT-PCR revealed overexpression of (Linc01282, lnc-MYADM-1:1, ZNF347, XIAP) and downregulation of (Lnc-atp12a-1:1, SIK1 and miR-616-3p). In CRC, bioinformatic research revealed many unique ceRNA networks centered on miR-616-3p that were previously unknown.Conclusion: This work reveals novel, previously unreported lncRNAs as prognostic biomarkers for CRC, as well as potential mRNAs as new therapeutic targets and predictive biomarkers for CRC. Furthermore, our analysis identified novel ceRNA networks that need be investigated further in CRC.
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