1.3.2 CeRNA
Competitive endogenous RNA (ceRNA) reveals a novel role of RNA-RNA interaction, which has been heavily studied in recent years. At the post-transcriptional level, miRNA attaches to the miRNA response element (MRE) at the 3’-UTR end of the target gene and suppresses translation. While certain lncRNAs produce MREs as well as function as miRNA sponges, competing to other targeted mRNAs. The ceRNA mechanism refers to the competitive binding between lncRNAs and mRNAs[17]. Other RNAs, such as mRNA, pseudogenes, and circRNA also can serve in this way as ceRNA[18].
LncRNA Sox2ot from exosomes derived from highly invasive tumor cells, binding to miR-200 as ceRNA mechanism, upregulate Sox2, to induce epithelial-mesenchymal transition (EMT) and stem cell like properties in different tumor cells, plays important roles in pancreatic ductal adenocarcinoma invasion and metastasis[19]. Lnc SNHG1 promote neuroinflammation, and neuronal toxicity via different mechanisms,in the process of Alzheimer’s disease, it could act as ceRNA for miR-137, targeting KREMEN1 in the human primary neuron (HPN) cells, reduce cell viability, promote cell apoptosis, decrease mitochondrial membrane potential and the protein levels of cytochrome C[20].
Whereas, there are some reports claiming that ceRNA only performs a slight role in miRNA regulation, single ceRNA is unlikely to have any biologically significant effects on the activity of miRNAs, or the expression of genes[11, 21]. Most of RBP and miRNAs regulate gene expression post-transcriptional have thousands of binding sites, the numbers of these binding sites are highly dynamic as transcription renders, only strong binding sites are likely to be altered by this crosstalk effect[22].
1.3.3 LncRNA co-expresses with miRNA as a pri-miRNA
Some miRNAs host genes can encode both lncRNA and miRNA, one of the functions of this class of lncRNAs is to act as primary miRNA, termed lnc-pri-miRNAs, able to produce miRNAs[23]. Among them, lnc LOC646329 can act as both a pri-miRNA to produce miR-29a/b1, and a transcriptional enhancer to activate neighboring oncogenes and promote Glioblastoma cell proliferation[24]. The genomic organization of lnc MIR100HG, is located on human chromosome 11 (hsa chr11),generate miR-100 and miR-125b,which co-represses several Wnt/β-catenin negative regulators,to rescue cetuximab responsiveness of cetuximab-resistant colorectal cancer and head and neck squamous cell cancer cell lines[25].