Identification of a novel intergenic miRNA located between the human DDC and COBL genes with a potential function in cell cycle arrest

Abstract

Frequent abnormalities in 7p12 locus in different tumors like lung cancer candidate this region for novel regulatory elements. MiRNAs as novel regulatory elements encoded within the human genome are potentially oncomiRs or miR suppressors. Here, we have used bioinformatics tools to search for the novel miRNAs embedded within human chromosome 7p12. A bona fide stem loop (named mirZa precursor) had the features of producing a real miRNA (named miRZa) which was detected through RT-qPCR following the overexpression of its precursor. Then, endogenous miRZa was detected in human cell lines and tissues and sequenced. Consistent to the bioinformatics prediction, RT-qPCR as well as dual luciferase assay indicated that SMAD3 and IGF1R genes were targeted by miRZa. MiRZa-3p and miRZa-5p were downregulated in lung tumor tissue samples detected by RT-qPCR, and mirZa precursor overexpression in SW480 cells resulted in increased sub-G1 cell population. Overall, here we introduced a novel miRNA which is capable of targeting SMAD3 and IGF1R regulatory genes and increases the cell population in sub-G1 stage.

A novel miRNA located in the GATA4 gene regulates the expression of IGF‐1R and AKT1/2 genes and controls cell proliferation

“…Despite the great advances made in the field of RNA sequencing and related bioinformatics tools, novel functional RNA transcripts are still being added to the bank of RNA families . Relying on our previous successful discovery of novel miRNAs within important genes, we intended to search the GATA4 gene sequence for novel miRNA(s). Bioinformatics analysis suggested 90 stem‐loop structures within this genomic region, one of which, we named GATA4‐miR1 precursor, is located in the second intron of the gene and was chosen for further validations (Figure A).…”

Identification of lncRNAs associated with lung squamous cell carcinoma prognosis in the competitive endogenous RNA network

“…In addition, four mRNAs (DDC, FGF9, GSG1, and LEFTY2) were considered to be significant for the overall survival of LUSC patients as verified by information from the GEO database. DDC, is a dopa deacidase, the expression of which is related to the biochemistry of many human cancers (Hoballa et al, 2018). Based on a number of previous studies, the expression of FGF9 showed carcinogenicity in human tumors (Hegab et al, 2018).…”

Exosomal microRNAs in regulation of tumor cells resistance to apoptosis

“…In some cases, there is nearly complete complementarity, which results in mRNA degradation and cleavage [ 18 , 19 ]. It has been shown that these molecules can act as oncogenes or tumor suppressors in cancers [ 20 , 21 ]. Moreover, miRNAs regulate cell differentiation, proliferation, and apoptosis by interacting with cancer target genes [ 22 ].…”