MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood.We evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures.We detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis.These findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO. 

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Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

Fusion genes are thought to be somatic and cause cancer, including acute myeloid leukemia (AML). Validating highly-recurrent fusion genes in healthy samples compelled us to systematically study hereditary fusion genes (HFGs). Here, we used curated HFGs to analyze AML fusion genes, and we identified 243 HFGs associated with AML inheritance from 926 potential HFGs. Many HFGs were one-to-many and many-to-one fusions that augmented signals from environmental and genomic alterations and seemed to support the “two-hit” hypothesis. The most highly-recurrent HFGs were also observed in multiple myeloma and monozygotic twin datasets, suggesting that AML is a complex genetic disease. HFGs, as cancer genetic biomarkers, are the most basic foundations for future genetic and genomic studies.

Hereditary Fusion Genes Are Associated with the Inheritance of Acute Myeloid Leukemia

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Comparative RNA-Sequencing Analysis Reveals High Complexity and Heterogeneity of Transcriptomic and Immune Profiles in Hepatocellular Carcinoma Tumors of Viral (HBV, HCV) and Non-Viral Etiology

Abstract Several bioinformatics studies have been performed on high‐throughput expression data to determine the cellular pathways and hub genes affected by Gastric cancer (GC). However, these studies differ in using a healthy tissue or normal tissue adjacent to the tumour (NAT) as calibrator tissues. This study was designed to find how using healthy or NAT tissues as calibrator tissues could affect pathway enrichment data and hub genes in GC. Two gene expression datasets with NAT tissues (GSE79973 and GSE118916) and one dataset with healthy tissues (GSE54129) were downloaded and processed by the limma package to screen the differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis were performed by the Enrichr online tool. Protein‐protein interaction network construction, module analysis, and hub genes selection were performed by Cytoscape software, Molecular Complex Detection plugin, and cytoHubba plugin, respectively. The gene expression profiling interactive analysis web server was used to analyse RNA sequencing expression data from The Cancer Genome Atlas Program. The Kaplan—Meier plotter was used to perform survival analysis. Our results showed that some KEGG and GO pathways were shared between studies with NAT and the study with healthy tissues. However, some terms, especially inflammation‐related terms, were missed when NAT tissues were used as calibrator tissues. Also, only FN1 and COL1A1 are common hub genes between DEGs of the studies with NAT and healthy tissues. Since hub genes are usually extracted and suggested as candidate targets for GC diagnosis, prognosis, or treatment, selecting healthy or NAT tissues may affect the hub genes selection.

Hub genes and pathways in gastric cancer: A comparison between studies that used normal tissues adjacent to the tumour and studies that used healthy tissues as calibrator

Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers and hence changes the cytoskeleton to affect the invasiveness and metastasis of tumors. This study aimed to investigate the function and clinical significance of ACTB in pan-cancer. The role of ACTB for prognosis and immune regulation across 33 tumors was explored based on the datasets of gene expression omnibus and the cancer genome atlas. Differential expression of ACTB was found between cancer and adjacent normal tissues, and significant associations was found between ACTB expression and prognosis of tumor patients. In most cancers, ACTB expression was associated with immune cells infiltration, immune checkpoints and other immune modulators. Relevance between ACTB and metastasis and invasion was identified in various types of cancers by CancerSEA. Moreover, focal adhesion and actin regulation-associated pathways were included in the functional mechanisms of ACTB. The expression of ACTB was verified by quantitative real-time polymerase chain reaction. Knockdown of ACTB inhibited head and neck squamous carcinoma cell migration and invasion by NF-κB and Wnt/β-catenin pathways. Our first pan-cancer study of ACTB offers insight into the prognostic and immunological roles of ACTB across different tumors, indicating ACTB may be a potential biomarker for poor prognosis and immune infiltration in cancers, and the role of ACTB as a reference gene in cancers was challenged.

Shouyi Tang

Papers

A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers.

Identification of key miRNAs and targeted genes involved in the progression of oral squamous cell carcinoma