Expression and clinical significance of FOS-like antigen 1 in gastric adenocarcinoma

BackgroundThe overexpression of FOS-like antigen 1 (FOSL1) in several types of cancers was reported before. However, the expression and clinical significance of FOSL1 in gastric cancer (GC) have not been elucidated.Materials and methodsThe expression of FOSL1 in 105 cases of GCs was detected with immunohistochemistry, and the mRNA of FOSL1 was investigated with quantitative real-time polymerase chain reaction(qRT-PCR) in 15 pairs of GCs and tumor adjacent tissues. With Chi-square test or Fisher test, we analyzed the correlation between FOSL1 expression and clinicopathological factors. With univariate analysis, we evaluated the correlations between clinicopathological factors including FOSL1 and overall survival (OS) rates. With multivariate analysis, we identified the independent prognostic risk factors of GC.ResultsThe percentages of patients with low and high FOSL1 expression in our study accounted for 43.81% and 56.19%, respectively. The mRNA levels of FOSL1 in GCs were significantly higher than those in tumor adjacent tissues. FOSL1 expression was demonstrated to be significantly correlated with lymphatic invasion (P = 0.036) and TNM stage (P = 0.016). High expression of FOSL1 was significantly correlated with lower 5-year OS (P = 0.002), and FOSL1 expression was identified as an independent prognostic biomarker of GC (P = 0.001).ConclusionsFOSL1 is an independent prognostic biomarker of GC. Detecting FOSL1 expression could help stratify GC patients with high-risk and guide the precious treatment.     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

LINC00205 promotes proliferation,migration and invasion of HCC cells by targeting miR-122-5p

Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in the tumorigenesis and progression of hepatocellular carcinoma (HCC). Recently, long intergenic non-protein coding RNA 205 (LINC00205) has been identified as a prognostic biomarker in HCC. However, the biological role of LINC0205 and its potential molecular mechanism are poorly investigated. Here, we found that the expression of LINC00205 was dramatically up-regulated in HCC tissues compared to adjacent nontumor tissues. Furthermore, the level of LINC00205 in both Hep3B and Huh7 cells was prominently higher than that in normal hepatic cell line LO2. Notably, the high expression of LINC00205 was strongly correlated with tumor size ≥5 cm, venous infiltration and advanced tumor stages. Functionally, LINC00205 knockdown obviously repressed the proliferation, migration and invasion of Hep3B and Huh7 cells in vitro. An inverse correlation between LINC00205 and miR-122-5p was detected in HCC tissues. Interestingly, LINC00205 knockdown increased the level of miR-122-5p in both Hep3B and Huh7 cells. Mechanistically, luciferase reporter assay demonstrated LINC00205 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-122-5p. More importantly, miR-122-5p overexpression significantly restrained the proliferation, migration and invasion of HCC cells. Collectively, our study provides solid evidence to support the oncogenic role of LINC00205 in HCC, which may be benefit for the improvement of HCC therapy.     

CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer

Breast cancer is the most common malignant tumor among women in China, which seriously threatens women's physical and mental health. Tumorigenesis is closely related to the dysregulation of cell cycle. The cell cycle progression includes interphase and mitotic phase (M phase). Cyclin B1 is a key protein in regulating M phase, which is essential for the whole cell cycle progression. CyclinB1 can be degraded through ubiquitination mediated by the anaphase promoting complex/cyclosome (APC/C). However, the mechanism of how CyclinB1 is deubiquitinated in breast cancer still remains unclear. In this study, we discovered that CyclinB1 interacted with ubiquitin-specific peptidase 14 (USP14). Based on the deubiquitinating function of USP14, we detected the effect of USP14 on the ubiquitination of CyclinB1. Inhibiting the activity of USP14 or USP14 knockdown significantly increased the ubiquitination of CyclinB1. In accordance with this, knocking down USP14 arrested cell cycle at G2/M phase. Knocking down USP14 with siRNAs significantly inhibited the proliferation and migration of breast cancer cells. In conclusion, our study demonstrated that USP14 regulated the cell cycle of breast cancer cells by regulating the ubiquitination of CyclinB1, which will provide a solid theoretical basis for the development of anti-cancer drugs targeting USP14.     

Non-coding RNAs: Regulators of glioma cell epithelial-mesenchymal transformation

GBM (glioblastoma multiforme) is the most malignant form of glioma and is the most commonly occurring primary malignant brain tumour. GBM is difficult to completely excise, resulting in an extremely high recurrence rate. The occurrence of an aggressive glioma phenotype depends on EMT (epithelial-mesenchymal transformation), in which epithelial cells transform into mesenchymal cells by losing their cell-cell adhesion and polarity. NcRNAs (non-coding RNAs) play a significant role in the cellular progression from a normal phenotype to a cancerous phenotype. Recently, many studies have shown that there are two essential regulatory ncRNAs, miRNAs (microRNAs) and lncRNAs, which are closely related to EMT. In this review, we conducted a comprehensive investigation of the dysregulated lncRNAs and miRNAs in gliomas with particular attention to the function and regulatory mechanisms of several important lncRNAs and miRNAs, and we discussed their roles as glioma diagnostic and prognostic biomarkers and their potential clinical applications as therapeutic targets.     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

Expression of co-inhibitory molecules B7-H4 and B7-H1 in Epstein-Barr virus positive diffuse large B-cell lymphoma and their roles in tumor invasion

To investigate the relationship between immunoregulatory molecules B7-H4 and B7-H1 in Epstein-Barr positive diffuse large B-cell lymphoma (EBV⁺DLBCL). Immunohistochemistry was used to detect the expression of B7-H4 and B7-H1 in tumor tissues of 13 patients with EBV⁺DLBCL. The expression levels of B7-H4 and B7-H1 in four diffuse large B-cell lymphoma cell lines (SU-DHL-4, SU-DHL-10, SU-DHL-6, Pfeiffer) were analyzed by flow cytometry. Transwell invasion assays were conducted to observe the invasive ability of cell lines. B7-H4 and B7-H1 were expressed in 84.62% and 100% tumor specimens of EBV⁺DLBCL. The overexpression of B7-H4 and B7-H1 was found in 46.15% and 23.08% tumor samples of EBV⁺DLBCL. There was a medium negative correlation between the expression levels of B7-H4 and B7-H1 (r = -0.667, P = 0.013, spearman rank correlation). The expression levels of B7-H1 in four diffuse large B-cell lymphoma cell lines were positively correlated with their invasive ability, whereas the expression levels of B7-H4 were not. Here, we provide evidence for the negative relationship between B7-H4 and B7-H1 in EBV⁺DLBCL. The expression of B7-H1 in EBV⁺DLBCL appears to be the dominant factor which affects tumor aggressiveness. When B7-H1 expression weakens, the molecule B7-H4 may become the dominant factor of prognosis in patients with EBV⁺DLBCL.     

Dysregulation of microRNA-106a-5p-RUNX1 axis associates with clinical progression and prognosis of osteosarcoma patients

MicroRNA-106a-5p (miR-106a-5p) functions as a tumor suppressor in osteosarcoma cells. Here, we aimed to identify novel target genes of miR-106a-5p in osteosarcoma, as well as to investigate their prognostic value and the biological functions. At first, the mammalian runt-related factor 1 (RUNX1) was identified as one of the target genes of miR-106a-5p in osteosarcoma cells by luciferase reporter gene assay, real-time quantitative RT-PCR and Western blot analysis. Then, the expression levels of miR-106a-5p and RUNX1 in osteosarcoma tissues were detected, and their associations with clinicopathological features and patients' prognosis were statistically analyzed. Compared with adjacent non-cancerous tissues, miR-106a-5p and RUNX1 mRNA/protein expression in osteosarcoma tissues were significantly decreased and increased, respectively (all P < 0.01). Low miR-106a-5p, high RUNX1 and miR-106a-5p-low/RUNX1-high expression in osteosarcoma tissues were all significantly associated with advanced Enneking stage, positive metastasis and shorter overall survival (all P < 0.05). Moreover, miR-106a-5p and RUNX1 expression, alone or in combination, were identified as independent prognostic factors for osteosarcoma patients' overall survival. Functionally, the enforced expression of miR-106a-5p significantly suppressed proliferation and invasion of osteosarcoma cells, while the overexpression of RUNX1 effectively reversed its suppressive roles. In conclusion, our findings show the dysregulation of miR-106a-5p-RUNX1 axis in human osteosarcoma tissues and suggest its crucial roles in cancer progression and patients' prognosis. More interestingly, miR-106a-5p may function as a tumor suppressor in osteosarcoma cells via regulating its target gene RUNX1.