Corrigendum: CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration.

[This corrects the article DOI: 10.3389/fonc.2019.00477.].

CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration.

Background/Aims: Recently, rapidly accumulating evidence has shown that microRNAs (miRNAs) are involved in human tumorigenesis, and the dysregulation of miRNAs has been observed in many cancers, including prostate cancer. miR-145-5p, an miRNA with reduced expression in prostate cancer cells, has been shown to have a tumor suppressive role in a variety of tumors. However, its underlying mechanism requires further elucidation. Methods: A lentiviral expression vector for miR-145-5p was constructed and used to establish a stable cell line (LNCaP) expressing miR-145-5p. The cells were cultured normally and divided into the control group (control), negative control group (negative control), and test group (miR-145-5p). Inhibition of proliferation was measured by a WST-8 assay. The early apoptosis rate of cells was detected by flow cytometry. Clone formation ability was detected by a clone formation inhibition test. Cell invasion and migration capacity was detected by a Transwell assay. The relative expression levels of proteins were detected by western blotting. We constructed a nude mouse model of prostate cancer to observe the effect of miR-145-5p on the growth of transplanted tumors. TargetScan bioinformatics software was used to predict target genes regulated by miR-14-5p. ChIPBase was used to predict transcription factors with binding sites in the upstream promoter region of miR-145-5p. Quantitative reverse transcription PCR was used to detect the relative expression level of genes. A bifluorescence-reporter gene vector was constructed to confirm the regulation of target genes by miR-145-5p. We used 5' rapid amplification of cDNA ends to confirm the transcription start site of miR-145-5p.Chromatin immunoprecipitation technology was used to detect the effect of transcription factors binding to miR-145-5p. Results: The overexpression of miR-145-5p not only inhibited the proliferation, invasion, and migration of LNCaP cells but also promoted their early apoptosis. After overexpressing miR-145-5p, the expression of small ubiquitin-like modifier protein-specific protease 1 (SENP1), and caudal-related homeobox 2 (CDX2) protein was decreased in LNCaP cells. The transcription factor CDX2 bound to the miR-145-5p promoter region and inhibited its transcription. The transcription start site of miR-145-5p was located at a guanine residue 1,408 bp upstream of the stem-loop sequence. Upon overexpression, miR-145-5p could bind to the 3'-untranslated region of SENP1 to inhibit its translation. Conclusion: These results suggested that CDX2 inhibits the expression of miR-145-5p, thereby relieving the inhibitory effect of miR-145-5p on the translation of SENP1 and affecting the invasion and migration of prostate cancer cells.

Gene-gene interaction network analysis of hepatocellular carcinoma using bioinformatic software.

Information processing tools and bioinformatics software have markedly advanced the ability of researchers to process and analyze biological data. Data from the genomes of humans and model organisms aid researchers to identify topics to study, which in turn improves predictive accuracy, facilitates the identification of relevant genes and simplifies the validation of laboratory data. The objective of the present study was to investigate the regulatory network constituted by long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNA in hepatocellular carcinoma (HCC). Microarray data from HCC datasets were downloaded from The Cancer Genome Atlas database, and the Limma package in R was used to identify the differentially expressed genes (DEGs) between HCC and normal samples. Gene ontology enrichment analysis of DEGs was conducted using the Database for Annotation, Visualization, and Integrated Discovery. TargetScan, microcosm, miRanda, miRDB and PicTar were used to predict target genes. lncRNAs associated with HCC were probed using the lncRNASNP database, and a lncRNA-miRNA-mRNA regulatory network was visualized using Cytoscape. The present study identified 114 differentially expressed miRNAs and 2,239 differentially expressed mRNAs; of these, 725 were downregulated genes that were primarily involved in complement and coagulation cascades, fatty acid metabolism and butanoate metabolism, among others. The remaining 1,514 were upregulated genes principally involved in DNA replication, oocyte meiosis and homologous recombination, among others. Through the integrated analysis of associations between different types of RNAs and target gene prediction, the present study identified 203 miRNA-mRNA pairs, including 28 miRNAs and 170 mRNAs, and identified 348 lncRNA-miRNA pairs, containing 28 miRNAs. Therefore, owing to the association between lncRNAs-miRNAs-mRNAs, the present study screened out 2,721 regulatory associations. The data in the present study provide a comprehensive bioinformatic analysis of genes, functions and pathways that may be involved in the pathogenesis of HCC.

Analyzing the LncRNA, miRNA, and mRNA Regulatory Network in Prostate Cancer with Bioinformatics Software.

Information processing tools and bioinformatics software have significantly advanced researchers' ability to process and analyze biological data. Molecular data from human and model organism genomes help researchers identify topics for study, which, in turn, improves predictive accuracy, facilitates the identification of relevant genes, and simplifies the validation of laboratory data. The objective of this study was to explore the regulatory network constituted by long noncoding RNA (lncRNA), miRNA, and mRNA in prostate cancer (PCa). Microarray data of PCa were downloaded from The Cancer Genome Atlas database and DESeq package in R language were used to identify the differentially expressed genes (DEGs) between PCa and normal samples. Gene ontology enrichment analysis of DEGs was conducted using the Database for Annotation, Visualization, and Integrated Discovery. TargetScan, microcosm, miRanda, miRDB, and PicTar were used to predict target genes. LncRNA associated with PCa was exploited in the lncRNASNP database, and the LncRNA-miRNA-mRNA regulatory network was visualized using Cytoscape. Our study identified 57 differentially expressed miRNAs and 1252 differentially expressed mRNAs; of these, 691 were downregulated genes primarily involved in focal adhesion, vascular smooth muscle contraction, calcium signaling pathway, and so on. The remaining 561 were upregulated genes principally involved in systemic lupus erythematosus, progesterone-mediated oocyte maturation, oocyte meiosis, and so on. Through the integrated analysis of correlation and target gene prediction, our studies identified 1214 miRNA:mRNA pairs, including 52 miRNAs and 395 mRNAs, and screened out 455 lncRNA-miRNA pairs containing 52 miRNAs. Therefore, owing to the interrelationship of lncRNAs and miRNAs with mRNAs, our study screened out 19,075 regulatory relationships. Our data provide a comprehensive bioinformatics analysis of genes, functions, and pathways that may be involved in the pathogenesis of PCa.

Overexpression of Long Non-Coding RNA MEG3 Inhibits Proliferation of Hepatocellular Carcinoma Huh7 Cells via Negative Modulation of miRNA-664.

Evidence is accumulating that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis and dysregulated in many cancers, including hepatocellular carcinoma (HCC). Because lncRNAs can regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, lncRNAs are valuable biomarkers and therapeutic targets. Maternally expressed gene 3 (MEG3) is a lncRNA overexpressed in HCC cells that inhibits HCC progression, however, the mechanism remains largely unknown. Recently, a novel regulatory mechanism has been proposed in which RNAs can cross-talk with each other via competing for shared microRNAs (miRNAs). The proposed competitive endogenous RNAs could mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. In the current study, we demonstrated that MEG3 is down-regulated in HCC tissues. MEG3 over-expression imposes another level of post-transcriptional regulation, whereas MEG3 overexpression increase the expression of the miR-664 target gene, ADH4, through competitive "sponging" miR-664. In addition, NF-κB may affect transcription of MEG3 by directly binding to the promoter region. Our data revealed that NF-κB may affect the transcript of MEG3. MEG3 overexpression inhibited the proliferation of HCC cells, at least in part by affecting miR-664mediated regulation of ADH4. Together, these results suggest that MEG3 is a suppressor of tumor which acts in part through "sponging" miR-664. J. Cell. Biochem. 118: 3713-3721, 2017. © 2017 Wiley Periodicals, Inc.

Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells.

Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21-22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer cells was reduced by small interfering RNA (siRNA). Subsequently, the ability of LNCaP cell proliferation, invasion, and migration of PCa was compromised both in vivo and in vitro with the occurrence of cell autophagy. Recently, a novel regulatory mechanism has been proposed in which RNAs cross talk via competing with the shared microRNAs (miRNAs). In addition, lncRNAs can directly interact with RNA-binding proteins and then bind to the gene promoter region to further regulate gene expression. The proposed competitive endogenous RNAs mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. Here, we demonstrated that binding of Snail to the promoter region of PCA3 could activate the expression of PCA3. Down-regulation of PCA3 by silencing could increase the expression of the miRNA-1261, which then targeted at the PRKD3 gene (protein kinase D3) through competitive sponging. In summary, these results suggest that the transcription factor, Snail, activated the expression of lncRNA PCA3, which could inhibit the translation of PRKD3 protein via competitive miR-1261 sponging, and thus high expression of PRKD3 further promoted invasion and migration of prostate cancer.