No abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, candidate genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with regulatory pathways in cancer. Ten hub genes (TTK, AURKB, KIF20A, KIF23, CEP55, CDC6, DTL, NCAPG, CENPF, PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significance p-values. At the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic markers for HCC.

The third most common malignancy has been identified as Colorectal cancer (CRC) that conducive to death in most cases. Chemoresistance is a common obstacle to CRC treatment. Circulating exosomal microRNAs (miRNAs) have been shown to reverse chemo‐resistance and are promising biomarkers for CRC. The capacity of engineered exosomes to cross biological barriers and deliver functional miRNAs could be used to achieve these proposes. The object of this review is the investigation of the role of exosomal miRNA in the chemo‐resistance, diagnosis, and prognosis of CRC. Using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, electronic databases, PubMed, EMBASE, Web of Science, Scopus were searched from January 1990 to November 2020. Ultimately, eight articles included five in vitro (16 cell lines) and three in vivo examinations. Three studies demonstrated that increasing or decreasing mRNA expression was associated with increasing and decreasing cell proliferation in vitro. The presence of miRNA in two studies increased the sensitivity of the drug and exhibited a considerable growth inhibitory effect on cancer cell proliferation. The apoptotic rate was significantly increased in four studies by increased mRNA expression and reduced mrna expression. Tumor volume of xenograft models in three studies suppressed by antitumor miRNA activity. In contrast, anti‐miRNA activity in one study decreased the tumor volume. Exosomal miRNAs can be regulators of chemo‐resistance and predict adverse outcomes in CRC patients. In sum, exosomes containing miRNAs can be a promising biomarker for the prognosis and diagnosis of CRC. Subsequent research should be a focus on delineating the function of exosomal miRNA before clinical use.

Thyroid cancer (TC) is the most common endocrine cancer, accounting for 1.7% of all cancer cases. It has been reported that the existing approach to diagnosing TC is problematic. Therefore, it is essential to develop molecular biomarkers to improve the accuracy of the diagnosis. This study aimed to screen hub lncRNAs in the ceRNA network (ceRNET) connected to TC formation and progression based on the overall survival rate. In this study, first, RNA‐seq data from the GDC database were collected. A package called edgeR in R programming language was then used to obtain differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) in TC patients' samples compared to normal samples. Second, DEmRNAs were analyzed for their functional enrichment. Third, to identify RNAs associated with overall survival, the overall survival of these RNAs was analyzed using the Kaplan‐Meier plotter database to create a survival associated with the ceRNA network (survival‐related ceRNET). Next, the GeneMANIA plugin was used to construct a PPI network to better understand survival‐related DEmRNA interactions. The survival ceRNET was then visualized with the Cytoscape software, and hub genes, including hub lncRNAs and hub mRNAs, were identified using the CytoHubba plugin. We found 45 DElncRNAs, 28 DEmiRNAs, and 723 DEmRNAs among thyroid tumor tissue and non‐tumor tissue samples. According to KEGG, GO and DO analyses, 723 DEmRNAs were mainly enriched in cancer‐related pathways. Importantly, the results found that ten DElncRNAs, four DEmiRNAs, and 68 DEmRNAs are associated with overall survival. In this account, the PPI network was constructed for 68 survival‐related DEmRNAs, and ADAMTS9, DTX4, and CLDN10 were identified as hub genes. The ceRNET was created by combining six lncRNAs, 109 miRNAs, and 22 mRNAs related to survival using Cytoscape. in this network, ten hub RNAs were identified by the CytoHubba plugin, including mRNAs (CTXND1, XKRX, IGFBP2, ENTPD1, GALNT7, ADAMTS9) and lncRNAs (AC090673.1, AL162511.1, LINC02454, AL365259.1). This study suggests that three lncRNAs, including AL162511.1, AC090673.1, and AL365259.1, could be reliable diagnostic biomarkers for TC. The findings of this study provide a basis for future studies on the therapeutic potential of these lncRNAs.

Background: As the most prevalent endocrine cancer, thyroid cancer (TC) accounts for 1.7% of all cancer cases. A significant increase in TC morbidity has been observed over the past three decades. TC diagnosis has been reported to be problematic based on the current approach. As a result, it is imperative to develop molecular biomarkers to improve the accuracy of the diagnosis. An analysis of bioinformatics data was conducted in this study to analyze lncRNAs and their roles as ceRNAs associated with the development and progression of TC. Materials and Method: The first step in this study was to collect RNA-seq data from the GDC database. Then, DESeq2 was used to analyze differentially expressed lncRNAs (DElncRNAs), miRNAs (DEMIs), and mRNAs (DEGs) between TC patients and healthy subjects. Our study identified DElnc-related miRNAs and miRNA-related genes to develop a lncRNA/miRNA/mRNA axis using online tools and screening. A co-expression analysis was performed to investigate correlations between DElncs and their associated mRNAs. Next, a protein-protein interaction (PPI) network was constructed. Functional enrichment and pathway enrichment were conducted on genes in the PPI network to discover additional biological activities among these molecules. Lastly, a correlation between the expression levels and the infiltration abundance of immune cells was assessed through immune infiltration analysis. Results: There were 58 DElncs, 34 DEMIs, and 864 DEGs in thyroid tumor tissue and non-tumor tissue samples. Following validation of our lncRNA results with the intersection of differentially expressed lncRNAs in TCGA and GEPIA2, we selected two downregulated DElncs, including AC007743.1 and LINC00092, as the final research elements. We then performed an interaction analysis to predict lncRNAs-miRNAs and miRNAs-mRNAs interactions, which led to identifying the LINC00092/miR-34a-5p and miR-34a-5p/RCAN1 axis, respectively. There was a correlation between LINC00092 and RCAN1 according to Pearson correlation analysis. To improve our understanding of RCAN1, we developed a PPI network. According to the Immune Infiltration Analysis, RCAN1 expression was positively correlated with CD8+ T cells, macrophages, and neutrophils. Conclusion: The results of this study suggest that LINC00092/miR-34a-5p/RCAN1 axis may have a functional role in the progression of TC. LINC00092 may be used as a promising biomarker for TC prognosis and may be a better diagnostic and therapeutic target.