As a pleiotropic cytokine, interleukin-6 (IL-6) not only regulates the cellular immune response, but it also promotes tumor development by activating multiple carcinogenic pathways. IL-6 expression is significantly elevated in colorectal cancer (CRC) and is closely related to CRC development and patient prognosis. In CRC, IL-6 activates signal transducers and activators of transduction-3 (STAT3) to promote tumor initiation and tumor growth. IL-6/STAT3 signalling has a profound effect on tumor-infiltrating immune cells in the tumor immune microenvironment in CRC. Additionally, IL-6/STAT3 pathway activates downstream target genes to protect tumor cells from apoptosis; drive tumor cell proliferation, cell cycle progression, invasion and metastasis; promote tumor angiogenesis; and stimulate drug resistance. Therefore, a thorough understanding of the many effects of the IL-6/STAT3 pathway in CRC is needed, which the present review examines.

EIF4A3, a member of the DEAD-box protein family, is a nuclear matrix protein and a core component of the exon junction complex (EJC). Under physiological conditions, EIF4A3 participates in post-transcriptional gene regulation by promoting EJC control of precursor mRNA splicing, thus influencing nonsense-mediated mRNA decay. In addition, EIF4A3 maintains the expression of significant selenoproteins, including phospholipid hydroperoxide glutathione peroxidase and thioredoxin reductase 1. Several recent studies have shown that EIF4A3 promotes tumor growth in multiple human cancers such as glioblastoma, hepatocellular carcinoma, pancreatic cancer, and ovarian cancer. Molecular biology studies also showed that EIF4A3 is recruited by long non-coding RNAs to regulate the expression of certain proteins in tumors. However, its tumor-related functions and underlying mechanisms are not well understood. Here, we review the physiological role of EIF4A3 and the potential association between EIF4A3 overexpression and tumorigenesis. We also evaluate the protein’s potential utility as a diagnosis biomarker, therapeutic target, and prognosis indicator, hoping to provide new ideas for future research.

With completing the whole genome sequencing project, awareness of lncRNA further deepened. The growth arrest-specific transcript 5 (GAS5) was initially identified in growth-inhibiting cells. GAS5 is a lncRNA (long non-coding RNA), and it plays a crucial role in various human cancers. There are small ORFs (open reading frames) in the exons of the GAS5 gene sequence, but they do not encode functional proteins. In addition, GAS5 is also the host gene of several small nucleolar RNAs (snoRNA). These snoRNAs are believed to play a suppressive role during tumor progression by methylating ribosomal RNA (rRNA). As a result, GAS5 expression levels in tumor tissues are significantly reduced, leading to increased malignancy, poor prognosis, and drug resistance. Recent studies have demonstrated that GAS5 can interact with miRNAs by base-pairing and other functional proteins to inhibit their biological functions, impacting signaling pathways and changing the level of intracellular autophagy, oxidative stress, and immune cell function in vivo. In addition, GAS5 participates in regulating proliferation, invasion, and apoptosis through the above molecular mechanisms. This article reviews the recent discoveries on GAS5, including its expression levels in different tumors, its biological behavior, and its molecular regulation mechanism in human cancers. The value of GAS5 as a molecular marker in the prevention and treatment of cancers is also discussed.

Overexpression of Golgi membrane protein 1 (GOLM1) is closely associated with hepatocellular carcinoma (HCC) vascular invasion. How GOLM1 may be involved in angiogenesis in HCC remains unclear. We explored how GOLM1 promotes angiogenesis in HCC and potential prognostic value. Expression levels of GOLM1 in HCC patients and healthy controls were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) between HCC patients and controls were compared. GOLM1 was knocked out in the HCC cell line, and RNA sequencing and DEG expression analysis were performed compared with control cells. Based on TCGA data and cell line RNA sequencing data, DEGs affected by a high expression of GOLM1 were identified. Subsequently, enrichment analysis was performed to explore the functions and pathways of the DEGs affected by a high expression of GOLM1. A relevant network analysis was built. Cox regression, genomic variance analysis scores, minimum absolute shrinkage and selection operator regression, and random forest regression models were applied to determine the best prognostic model and validated using the GSE54236 dataset from the Gene Expression Omnibus (GEO). We determined the effect of GOLM1 expression on immune cell infiltration in liver cancer. GOLM1 was overexpressed in HCC tissues compared with controls, and its level correlated with tumor purity and prognosis. 400 DEGs affected by highly expressed GOLM1 were identified in TCGA and cell line RNA sequencing data. Enrichment analysis revealed that these DEGs may be related to biological processes of oxidative stress and angiogenesis and involved in the VEGF signaling pathway and protein processing in endoplasmic reticulum. We predicted a comprehensive regulatory network in which GOLM1 activated VEGF signaling to promote HCC angiogenesis. GOLM1 may interact with E2F1 and IGF2BP3 to promote angiogenesis. GOLM1 overexpression was associated with greater immune cell infiltration. A random forest regression model was the best prognostic model. Our study reveals a potential molecular mechanism of GOLM1 in promoting HCC. We developed two prognostic models based on DEG associated with GOLM1 overexpression to help stratify HCC prognosis and improve individualized treatment.

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