Background Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N 6 -methyladenosine (m6A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cancer self-renewal and cell fate. However, the key enzymes of m6A expression and function in human breast carcinogenesis remain unclear. Methods The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC. Results The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival. Conclusions Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC. Electronic supplementary material The online version of this article (10.1186/s12885-019-5538-z) contains supplementary material, which is available to authorized users.

Lung cancer is the leading cause of cancer deaths in the world. Brain metastasis (BM) can affect about 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. MicroRNAs (miRNAs) play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment and prognosis. In this study, using RT-PCR and further northern blot validation, we confirmed that miR-378 was significantly differentially expressed in the matched NSCLC from 8 patients with BM and 21 without BM. Our study showed evidences that miR-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. MiR-378 may be a potential biomarker for characterizing non-small cell lung cancer brain metastasis and assisting clinicians in stratifying the high-risk patients on a clinical trial for either prophylactic cranial irradiation or a new intervention that may mitigate BM development, ultimately leading to a new standard of care for NSCLC patients.

Pyroptosis is a form of caspase-1-dependent programmed cell death with anti-tumor properties, but the underlying molecular mechanisms are not fully understood. The results of our study showed that the antihyperlipidemic drug simvastatin induced pyroptosis in non-small cell lung cancer (NSCLC) cell lines and a xenograft mouse model. Inhibition of pyroptosis attenuated the effects of simvastatin on tumor cell viability and migration. These data suggest that simvastatin may induce pyroptosis, thereby potentially serving as a novel therapeutic agent for NSCLC.

Ubiquitin-specific protease 22 (USP22), a novel ubiquitin hydrolase, has been implicated in oncogenesis and cancer progression in various types of human cancer. However, the clinical significance of USP22 expression in non-small cell lung cancer (NSCLC) has not been determined. In the present study, USP22 messenger RNA (mRNA) and protein levels were analyzed by quantitative real-time polymerase chain reaction (PCR) and western blot analysis in 30 cases of NSCLC and in corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect USP22 protein expression in 86 primary tumor tissues derived from clinically annotated NSCLC cases at stage I-II. In our analysis we found that both USP22 mRNA and protein levels in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues and that there was a significant correlation between the expression of USP22 mRNA and protein (P=0.000, κ=0.732). In addition, a high-level of USP22 expression was observed in 53.3% (39 out of 86) cases and it was correlated with large tumor size (P=0.029) and lymph node metastasis (P=0.026). Patients with tumors displaying a high-level of USP22 expression showed significantly shorter survival (P=0.006, log-rank test). Importantly, multivariate analysis showed that high USP22 protein expression was an independent prognostic factor for NSCLC patients (P=0.003). In sum, our data suggest that USP22 plays an important role in NSCLC progression at the early stage, and that overexpression of USP22 in tumor tissues could be used as a potential prognostic marker for patients with early clinical stage of NSCLC.

BackgroundOur aim was to investigate the influence of FTS on human cellular and humoral immunity using a randomized controlled clinical study in esophageal cancer patients.MethodsBetween October 2013 and December 2014, 276 patients with esophageal cancer in our department were enrolled in the study. The patients were randomized into two groups: FTS pathway group and conventional pathway group. The postoperative hospital stay, hospitalization expenditure, and postoperative complications were recorded. The markers of inflammatory and immune function were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (POD), including serum level of interleukin-6 (IL-6), C-reactive protein (CRP), serum globulin, immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA) and lymphocyte subpopulations (CD3 lymphocytes, CD4 lymphocytes, CD8 lymphocytes and the CD4/CD8 ratio) in the patients between the two groups.ResultsIn all, 260 patients completed the study: 128 in the FTS group and 132 in the conventional group. We found implementation of FTS pathway decreases postoperative length of stay and hospital charges (P < 0.05). In addition, inflammatory reactions, based on IL-6 and CRP levels, were less intense following FTS pathway compared to conventional pathway on POD1 and POD3 (P < 0.05). On POD1 and POD3, the levels of IgG, IgA, CD3 lymphocytes, CD4 lymphocytes and the CD4/CD8 ratio in FTS group were significantly higher than those in control group (All P < 0.05). However, there were no differences in the level of IgM and CD8 lymphocytes between the two groups.ConclusionsFTS improves postoperative clinical recovery and effectively inhibited release of inflammatory factors via the immune system after esophagectomy for esophageal cancer.Trial registrationChiCTR-TRC-13003562, the date of registration: August 29, 2013.