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BackgroundHepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear.Materials and methodsIn this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups.ResultsEight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy.ConclusionOur study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.

The lncRNA MIR4435-2 host gene (MIR4435-2HG) is located on human chromosome 2q13, and its expression is up-regulated in 18 tumors. MIR4435-2HG participates in 6 signaling pathways to promote tumorigenesis, including the TGF-β signaling pathway, Wnt/β-catenin signaling pathway, MDM2/p53 signaling pathway, PI3K/AKT signaling pathway, Hippo signaling pathway, and MAPK/ERK signaling pathway. MIR4435-2HG competitively binds with 20 miRNAs to form a complex ceRNA network, thereby regulating the expression of downstream target genes. The high expression of MIR4435-2HG is also closely related to the clinicopathological characteristics and poor prognosis of a variety of tumors. Also, the high expression of MIR4435-2HG in peripheral blood or serum has the value of predicting the risk of 9 tumors. In addition, MIR4435-2HG participates in the mechanism of action of three cancer drugs, including resveratrol for the treatment of lung cancer, cisplatin for non-small cell lung cancer and colon cancer, and carboplatin for triple-negative breast cancer. This article systematically summarizes the diagnostic and prognostic value of MIR4435-2HG in a variety of tumors and outlines the ceRNA network and signaling pathways related to MIR4435-2HG, which will provide potential directions for future MIR4435-2HG research.

Long non-coding RNA (lncRNA) is important in the study of cancer mechanisms. LINC00520 is located on human chromosome 14q22.3 and is a highly conserved long non-coding RNA. LINC00520 is widely expressed in various tissues. The expression of LINC00520 is regulated by transcription factors such as Sp1, TFAP4, and STAT3. The high expression of LINC00520 is significantly related to the risk of 11 cancers. LINC00520 can competitively bind 10 miRNAs to promote tumor cell proliferation, invasion, and migration. In addition, LINC00520 is involved in the regulation of P13K/AKT and JAK/STAT signaling pathways. The expression of LINC00520 is significantly related to the clinicopathological characteristics and prognosis of tumor patients and is also related to the sensitivity of HNSCC to radiotherapy. Here, this article summarizes the abnormal expression pattern of LINC00520 in cancer and its potential molecular regulation mechanism and points out that LINC00520 can be used as a potential biomarker for cancer diagnosis, prognosis, and treatment.

IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an important role in autoimmune diseases, inflammatory diseases and cancer. IL-10 is closely related to epigenetic modification, in which changes in DNA methylation of IL-10 gene can affect mRNA and protein levels of IL-10. In addition, changes in histone modifications, especially histone acetylation, can also lead to abnormal expression of IL-10 mRNA. At the same time, a handful of IL-10 related microRNAs (miRNAs) are found to be aberrantly expressed in multiple diseases. Besides, long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) also inhibits IL-10 expression. Here, we reviewed the epigenetic changes related to IL-10 in various diseases, as well as the regulation of IL-10 gene expression in various diseases by epigenetic modifications such as DNA methylation, histone modification, miRNA, and lncRNA.