Jie Zhu

Cholangiocarcinoma (CCA), a high mortality malignant carcinoma characterized by advanced disease and frequent recurrence, constitutes a major challenge for treatment and prognosis. AT-rich interaction domain 1A (ARID1A) variation is a distinct genetic entity in CCA, getting mounting concerns recently. Here, we comprehensively reviewed the clinical significance and molecular mechanisms of ARID1A alterations in CCA. Based on the independent data derived from 29 relevant studies, the variation rate of ARID1A in intrahepatic and extrahepatic CCA is reported at 6.9–68.2% and 5–55%, respectively. Most of the included studies (28/29, 96.6%) suggest that ARID1A serves as a tumor suppressor in CCA. ARID1A variation may be an important prognostic indicator to predict disease mortality, metastasis, and recurrence in patients with CCA. Multifactorial molecular mechanisms are involved in the relationship between ARID1A variations and the pathogenesis and pathophysiology of CCA, including disruption of the cell cycle, chromatin remodeling, oxidative stress damage, DNA hypermethylation, and the interaction of multiple genes being affected. This review describes that ARID1A variation might be a potential diagnostic and prognostic biomarker for CCA. Future diagnoses and treatments targeting ARID1A hint towards a precision medicine strategy in the management of CCA.

Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA‐miRNA pairs and miRNA‐mRNA pairs. Inflammation‐associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein‐protein interaction (PPI) networks of inflammation‐associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan‐Meier plotter databases, respectively. The circRNA_102049/miR‐455‐3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR‐455‐3p were explored by RT‐PCR, western blot, and dual‐luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR‐455‐3p and partially reversed the effect of miR‐455‐3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT‐related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up‐regulating the expression of MAP3K2 via sponging miR‐1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.

The present study investigated the underlying mechanisms and effects of toll‑like receptor 4 (TLR4) on a mouse model of allergic rhinitis (AR). An ovalbumin (OVA)‑induced mouse model of AR was treated with TLR4‑short hairpin RNA (shRNA). Allergic symptoms were then subsequently assessed. Protein levels of OVA‑specific immunoglobulin E (IgE), eosinophil cation protein (ECP), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in mice serum and nasal lavage fluid, as well as various inflammatory cytokine mediators in mice serum, were determined by ELISA. Protein level detection was performed using reverse transcription‑quantitative PCR and western blot analysis. The results revealed that TLR4 was highly expressed in the nasal mucosa of AR mice. TLR4 inhibition significantly relieved OVA‑induced AR symptoms. Relief of symptoms was evidenced by a decreased frequency of sneezing and nose friction, reduced levels of OVA‑specific IgE, ECP, LTC4, PGD2, less inflammatory cells and decreased levels of T‑helper 2 type cytokines. In addition, the data indicated that OVA‑induced activation of the NF‑κB pathway was repressed by TLR4‑shRNA. The results of the current study indicate that TLR4 may be a promising therapeutic target of AR.

The purpose of the present study was to investigate the serum levels of microRNA (miRNA/miR)-382-3p, -598-3p, -1246 and ‑184 in breast cancer patients and to assess their feasibility as biomarkers for breast cancer screening. Serum samples were obtained from 100 breast cancer patients and 40 age‑matched healthy control subjects in Taizhou Central Hospital (Taizhou, Zhejiang, China) between January 2013 and September 2014. The serum expression levels of miR‑382‑3p, ‑598‑3p, ‑1246 and ‑184 were determined by stem‑loop reverse transcription‑quantitative polymerase chain reaction. Receiver operating characteristic curves were drawn to evaluate the sensitivity and specificity of the serum miRNA expression levels for the screening of breast cancer. miR‑382‑3p and ‑1246 were significantly upregulated in the serum of the breast cancer patients, while miR‑598‑3p and ‑184 were significantly downregulated. The sensitivity and specificity to detect breast cancer were as follows: miR‑382‑3p, 52.0 and 92.5%; miR‑598‑3p, 95.0 and 85.0%; miR‑1246, 93.0 and 75.0%; and miR‑184, 87.5 and 71.0%, respectively. The expression levels of the four serum miRNAs were not correlated with the patients' clinical stage. In summary, miR‑382‑3p, ‑598‑3p, ‑1246 and ‑184 are all involved in the development of breast cancer, and are promising biomarkers for breast cancer detection.

To explore the effect of extracts of Prunella vulgaris L.on proteome of human lung adenocarcinoma cell line A549 by two-dimensional electrophoresis and mass spectrometry and elucidate the mechanism of anti-lung adenocarcinom effect of Prunella vulgaris L.at the level of proteome. The proliferative activity of human lung adenocarcinoma cell line A549 was evaluated by methyl thiazolyl tetrazolium (MTT) colorimetric assay. According to the difference of culture medium, all subjects were divided into the experimental group with culture medium of extracts of Prunella vulgaris L. (300 µg/ml) and the control group with culture medium of DMSO (0.3%). Proteins were isolated by two-dimensional electrophoresis and proteomic maps acquired by silver staining. And proteomic analysis was processed by Image Master 2D Quant Platinum 6.0. The proteins with > 2-fold differences were used to analyze by mass spectrometry and confirmed by Western blot. The expressions of inositol 1, 4, 5-triphosphate receptor-interacting protein-like 2 precursor, heat shock cognate protein 70, serine-threonine kinase receptor-associated protein, tropomyosin 2(β) isoform 1, cyclin B3, MED12L protein and macrophin 1 isoform 2 were higher in experimental group than those in control group (ratio (medicial/normal) 2.051 93, 1 000 001, 2.203 08, 5.042 01, 15.178 00, 1 000 001, 1 000 001) . And the expressions of enolase 1, M2-type pyruvate kinase, heat shock protein 27, Rho GDP-dissociation inhibitor 1, heat shock protein β1, TapasinERP57 heterodimer chain A, inorganic pyrophosphatase and mitochondrial Cysteinyl-tRNA synthetase 2 (putative) were lower in experimental group than those in control group (ratio (medicial/normal) 0.485 18, 0.491 53, 0.465 43, 0.454 71, 0.499 34, 0.450 36, 0.494 62, 0.437 33). The extracts of Prunella vulgaris L.have multi-target and multi-pathway effects on anti-lung adenocarcinoma. And its possible mechanisms may be due to the regulation of steady state of calcium ion, cell cycle and its steady state and the inhibition of tumor cell proliferation and metastasis.