New long noncoding RNA biomarkers and ceRNA networks on miR-616-3p in colorectal cancer: Bioinformatics-based study.

Background: Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR-616-3p. Materials and Methods: The gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1-built CeRNA networks. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9. Results: qRT-PCR showed (Linc01282, lnc-MYADM-1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt-inducible kinases 1 [SIK1], and miR-616-3p) were down regulated. Conclusion: These results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

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.

MicroRNAs regulating Wnt signaling pathway in colorectal cancer: biological implications and clinical potentials.

Colorectal cancer (CRC) is one of the most frequent cancers leading to death worldwide. Different signaling pathways such as the canonical Wnt signaling pathway have many effects on the development of CRC. MicroRNAs are small non-coding RNAs and different evidence represent their importance in the development of cancer via regulating the expression of their target genes. miRNAs can affect CRC progression as oncogenes or tumor suppressors. Dysregulation in miRNA expression can occur for various reasons, causes different abnormalities in the Wnt signaling pathway, and contributes to CRC development. Identifying the exact interactions between microRNAs and mRNAs or other non-coding RNAs assists in designing effective therapeutic, diagnostic, and prognostic approaches. In this review, we aim to focus on microRNAs that regulate CRC through modulating the Wnt pathway and then present the perspective outlook on the implication of miRNA in liquid biopsy for the management of patients with CRC.

Dysregulation of RNA interference components in COVID-19 patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals. RESULTS: Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.