Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family and localizes to the cytoplasm. STAT4 is phosphorylated after a variety of cytokines bind to the membrane, and then dimerized STAT4 translocates to the nucleus to regulate gene expression. We reviewed the essential role played by STAT4 in a wide variety of cells and the pathogenesis of diverse human diseases, especially many kinds of autoimmune and inflammatory diseases, via activation by different cytokines through the Janus kinase (JAK)-STAT signaling pathway.

Hepatocellular carcinoma (HCC) is one of the most notable lethal malignancies worldwide. However, the molecular mechanisms involved in the initiation and progression of this disease remain poorly understood. Over the past decade, many studies have demonstrated the important regulatory roles of long non-coding RNAs (lncRNAs) in HCC. Here, we comprehensively review recent discoveries regarding HCC-associated lncRNA functions, which we have classified and described according to their mechanism models.

C1ORF112 is an evolutionarily conserved gene across vertebrates. Over the last decade, studies have suggested that C1ORF112 may play a role in tumorigenesis. Using The Cancer Genome Atlas datasets, we explored the role of C1ORF112 across various tumor types in this study. In most tumor types, C1ORF112 expression was increased in tumor tissues compared to corresponding non-tumor tissues. In patients with certain tumor types, higher C1ORF112 expression was correlated with shorter overall survival, disease-free survival, and progression-free survival. Further analyses of C1ORF112 genetic alteration data showed that C1ORF112 amplification and mutations may have an impact on liver hepatocellular carcinoma and uterine corpus endometrial carcinoma prognosis. In cancers including lower grade glioma and adrenocortical carcinoma, C1ORF112 expression was linked to cancer-associated fibroblast infiltration. Gene Ontology analysis showed that C1ORF112 was co-expressed with genes involved in biological processes such as cell cycle and mitotic regulation. The protein interaction network demonstrated that C1ORF112 physically interacted with RAD51, DMC1, and FIGNL1, which have well characterized functions in DNA repair and cell cycle regulation. This pan-cancer study revealed the prognostic value and oncogenic role of C1ORF112 across multiple tumor types.

Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958 individuals and identify rs73613962 (T > G) within the intronic region of PRMT7 at 16q22.1 as a susceptibility locus of HCC (OR = 1.41, P = 6.02 × 10⁻¹⁰). An enhancer dual-luciferase assay indicates that the rs73613962-harboring region has allele-specific enhancer activity. CRISPR-Cas9/dCas9 experiments further support the enhancer activity of this region to regulate PRMT7 expression. Mechanistically, transcription factor HNF4A binds to this enhancer region, with preference to the risk allele G, to promote PRMT7 expression. PRMT7 upregulation contributes to in vitro, in vivo, and clinical HCC-associated phenotypes, possibly by affecting the p53 signaling pathway. This concept of HCC pathogenesis may open a promising window for HCC prevention/treatment.