Accumulating evidences indicated that tumor suppressor candidate 7 (TUSC7) is a putatively tumor suppressor gene in various tumors. We carried out current systematic review and meta-analysis to explore the decreased expression of TUSC7 associate with prognostic and clinicopathological characteristic in cancer patients. A literature collection search in the online electronic databases PubMed, Embase, Web of Science, and CNKI was conducted to obtain eligible studies (up to February 20, 2017). A total of nine studies comprise 757 patients were identified and included in present meta-analysis based on the selection and inclusion criteria. Overall, low expression of TUSC7 was associated with significantly unfavorable overall survival (OS) (HR = 2.90, 95% CI: 2.12-3.98, P < 0.001), disease free survival (DFS) (HR = 2.00, 95% CI: 1.49-2.68, P < 0.001) and disease-specific survival (DSS) (HR = 2.57, 95% CI: 1.23-5.39, P = 0.012) in tumors patients. Moreover, we also found that down-regulation of TUSC7 associated with distant metastasis (OR = 2.85, 95% CI: 1.46-5.55, P = 0.002) and larger tumor size (OR = 0.41, 95% CI: 0.23-0.72, P = 0.002). Our meta-analysis demonstrated that cancers patients detected with low TUSC7 expression were more prone to develop distant metastasis. TUSC7 might act as a potentially and promising common prognostic markers in some solid tumors.

In the treatment of early-stage rectal cancer, a growing number of studies have shown that transanal endoscopic microsurgery is one of the alternatives to radical surgery adhering to total mesorectal excision that can reduce the incidence of adverse events without compromising treatment outcomes. The purpose of this meta-analysis is to compare the safety and treatment effect of transanal endoscopic microsurgery and radical surgery adhering to total mesorectal excision to provide a basis for clinical treatment selections.

Ewing sarcoma is the second most common bone sarcoma in children, with 1 case per 1.5 million in the United States. Although the survival rate of patients diagnosed with localized disease is approximately 70%, this decreases to approximately 30% for patients with metastatic disease and only approximately 10% for treatment-refractory disease, which have not changed for decades. Therefore, new therapeutic strategies are urgently needed for metastatic and refractory Ewing sarcoma.

Mediastinal parathyroid carcinoma (PC) is a rare entity in primary hyperparathyroidism. The aim of this report is to demonstrate a case of mediastinal PC, and to provide a systemic literature review of this rare condition. A 34-year-old woman who had already undergone two cervical operations for hyperparathyroidism suffered from another recurrence, presenting with recurrent acute pancreatitis and persistent hypercalcemic crisis. Technetium-99 methoxyisobutylisonitrile imaging (MIBI) and computed tomography scanning (CT) identified three possible parathyroid tumors, one of which was the recurrence of residual tumor locating in the thyroid region, while the other two were ectopic tumors locating in the suprasternal fossa and thymus region, respectively. Pathological examination confirmed the diagnosis of PC. We conducted a systemic literature review by searching the PubMed MEDLINE from 1951 to 2019 for studies of all types in the English language only, using terms "mediastinal, mediastinum, parathyroid, carcinoma." Including our reported case, a total of 21 cases with ectopic mediastinal PCs were assessed for demographic data, tumor location and size, biochemical findings, and symptomatology, etc. Two thirds of the patients were men, with a mean age of 44 years old, a mean serum calcium of 14.2 mg/dl, and a mean serum intact parathyroid hormone of 1,216 pg/ml. We identified 89.5% of carcinomas in the anterosuperior mediastinum, and 10.5% in the middle mediastinum, with a mean diameter of 54 mm, and a mean weight of 216 g. MIBI and CT were the most commonly used methods to localize these mediastinal tumors, with 69.2 and 100% sensitivity, respectively. Half of the patients underwent more than one operation. Diagnosis and treatment of mediastinal PCs represent a challenge. Early suspicion, appropriate preoperative localization studies, and the cooperation of endocrinologists and surgeons are crucial in the effective management.

Osteonecrosis of the femoral head (ONFH) is a common, refractory and disabling disease of orthopedic department, which is one of the common causes of hip pain and dysfunction. Recent studies have shown that much progress has been made in the research of programmed cell death (PCD) in ONFH. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hot spots of PCD in ONFH through bibliometrics.

Gene single nucleotide polymorphisms (SNPs) have been extensively studied in association with development and prognosis of various malignancies. However, the potential role of genetic polymorphisms of cancer stem cell (CSC) marker genes with respect to cancer risk has not been examined. We conducted a case-control study involving a total of 1000 subjects (500 lung cancer patients and 500 age-matched cancer-free controls) from northeastern China. Lung cancer risk was analyzed in a logistic regression model in association with genotypes of four lung CSC marker genes (CD133, ALDH1, Musashi-1, and EpCAM). Using univariate analysis, the Musashi-1 rs2522137 GG genotype was found to be associated with a higher incidence of lung cancer compared with the TT genotype. No significant associations were observed for gene variants of CD133, ALDH1, or EpCAM. In multivariate analysis, Musashi-1 rs2522137 was still significantly associated with lung cancer when environmental and lifestyle factors were incorporated in the model, including lower BMI; family history of cancer; prior diagnosis of chronic obstructive pulmonary disease, pneumonia, or pulmonary tuberculosis; occupational exposure to pesticide; occupational exposure to gasoline or diesel fuel; heavier smoking; and exposure to heavy cooking emissions. The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.7686. To our knowledge, this is the first report to show an association between a Musashi-1 genotype and lung cancer risk. Further, the prediction model in this study may be useful in determining individuals with high risk of lung cancer.

Bcl-2 is critical for tumorigenesis. However, previous studies on the association of Bcl-2 promoter polymorphisms with predisposition to different cancer types are somewhat contradictory. Therefore, we performed this meta-analysis regarding the relationship between Bcl-2 promoter single nucleotide polymorphisms (SNPs) and cancer susceptibility and prognosis. Up to August 2016, 32 original publications were identified covering two Bcl-2 promoter SNPs (rs2279115 and rs1801018). Our results showed statistically significant association between rs2279115 and cancer susceptibility and prognosis in all four genetic models but not in rs1801018. Subgroups analysis indicated that rs2279115 was associated with a significantly higher risk of cancer susceptibility in Asia but not in Caucasian. Furthermore, rs2279115 was associated with a significantly higher risk in digestive system cancer and endocrine system cancer but not in breast cancer, respiratory cancer and hematopoietic cancer. Simultaneously, rs2279115 was correlated with a significantly higher risk of cancer prognosis in Asia but not in Caucasian. Considering these promising results, rs2279115 may be a tumor marker for cancertherapy in Asia. Sensitivity analysis show four gene model were stable, and no publication bias was observed in all four gene model. Large sample size, different ethnic population and different cancer type are warranted to validate this association.

The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.

Intellectual disability (ID) is one of the most prevalent chronic developmental brain disorders or phenotype of syndromic ID, affecting nearly 1-2% of the general population worldwide. Over recent decades, tremendous effort and high-throughput platforms have been devised to explore the complex heterogeneity, numerous genes and variants have been associated with the ID, especially de novo mutations and copy number variants. An organized resource containing the increasing genetic data is imperative to assist ID research. In this study, the integrative and annotated intellectual disability database has been developed, named 'IDGenetics', which contains known information about ID, including 815 genes and 17102 variants associated with 918 clinical diseases (3001 clinical phenotype) collected from 3822 publications and ID-related databases. Furthermore, in-depth data mining was performed to obtain an understanding of each entry, including functional annotation, gene/disease/phenotype network establishment and overlap analysis focusing on comorbidity. 1478 candidate genes (483 high-confidence and 995 low-confidence) were collected and prioritized by adopting the annotations of 12 functional prediction tools and algorithm. In addition, IDGenetics database provides concise search methods, convenient browsing functions, intuitive graphical displays and constantly updated features. IDGenetics will be a valuable and integrative resource for deciphering the genetic and functional architecture of ID and the improvement of clinical diagnosis, intervention and treatment.

Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Therefore, identifying the potential molecular mechanisms that promote HCC and CRC progression and metastasis are urgently needed. Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic enzyme that acetylates the high-order polyamines spermine and spermidine, thus decreasing the cellular content of polyamines. Several publications have suggested that depletion of intracellular polyamines inhibited tumor progression and metastasis in various cancer cells. However, whether and how SSAT regulates cell growth, migration and invasion in hepatocellular and colorectal carcinoma cells remains unclear. In this study, depletion of polyamines mediated by SSAT not only attenuated the tumor cell proliferation but also dramatically inhibited cell migration and invasion in hepatocellular and colorectal carcinoma cells. Subsequent investigations revealed introduction of SSAT into HepG2, SMMC7721 hepatocellular carcinoma cells and HCT116 colorectal carcinoma cells significantly suppressed p-AKT, p-GSK3β expression as well as β-catenin nuclear translocation, while inhibition of GSK3β activity or exogenous polyamines could restore SSAT-induced decreases in the protein expression of p-AKT, p-GSK3β and β-catenin. Conversely, knockdown of SSAT in Bel7402 hepatocellular carcinoma cells and HT-29 colorectal carcinoma cells which expressed high levels of SSAT endogenously significantly promoted the expression of p-AKT, p-GSK3β as well as β-catenin nuclear translocation. Taken together, our results indicated depletion of polyamines by SSAT significantly inhibited cell proliferation, migration and invasion through AKT/GSK3β/β-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells.

Elucidation of the mechanisms of stem cell differentiation is of great scientific interest. Increasing evidence suggests that stem cell differentiation involves changes at multiple levels of biological regulation, which together orchestrate the complex differentiation process; many related studies have been performed to investigate the various levels of regulation. The resulting valuable data, however, remain scattered. Most of the current stem cell-relevant databases focus on a single level of regulation (mRNA expression) from limited stem cell types; thus, a unifying resource would be of great value to compile the multiple levels of research data available. Here we present a database for this purpose, SyStemCell, deposited with multi-level experimental data from stem cell research. The database currently covers seven levels of stem cell differentiation-associated regulatory mechanisms, including DNA CpG 5-hydroxymethylcytosine/methylation, histone modification, transcript products, microRNA-based regulation, protein products, phosphorylation proteins and transcription factor regulation, all of which have been curated from 285 peer-reviewed publications selected from PubMed. The database contains 43,434 genes, recorded as 942,221 gene entries, for four organisms (Homo sapiens, Mus musculus, Rattus norvegicus, and Macaca mulatta) and various stem cell sources (e.g., embryonic stem cells, neural stem cells and induced pluripotent stem cells). Data in SyStemCell can be queried by Entrez gene ID, symbol, alias, or browsed by specific stem cell type at each level of genetic regulation. An online analysis tool is integrated to assist researchers to mine potential relationships among different regulations, and the potential usage of the database is demonstrated by three case studies. SyStemCell is the first database to bridge multi-level experimental information of stem cell studies, which can become an important reference resource for stem cell researchers. The database is available at http://lifecenter.sgst.cn/SyStemCell/.

Anterior cruciate ligament (ACL) injury experiences about 200,000 isolated cases annually, and ACL reconstruction has become the gold standard for the restoration of stability and functionality. In view of that incorrect graft placement is a common cause of ACL reconstruction failure, it is critically important to ensure that the tibial and femoral tunnels are properly placed during the operation. Therefore, we intend to conduct a network meta-analysis to comparatively evaluate the clinical outcomes among the different surgical techniques in ACL reconstruction.

Aurora B is aberrantly expressed in various tumors and shown to be a promising target for cancer therapy. Butein, a chalcone isolated from Rhus cerniciflua, has demonstrated antitumor activities in different cancers. In this study, we aimed to validate whether Aurora B kinase was the direct target of butein to exhibit its potency in hepatocellular carcinoma (HCC). Comparing with the normal cell line and tissue, Aurora B was overexpressed in all tested HCC cells and the majority of tumor tissue. Knocking down of Aurora B with shRNA substantially inhibited HCC cell proliferation, colony formation and delayed tumor growth in nude mice. Except computer docking, a series of kinase assays revealed butein directly interacted with Aurora B and inhibited its kinase activity. Along with the decrease of Aurora B and histone H3 phosphorylation, HCC cells were induced G2/M cell cycle arrest and subjected to cell apoptosis. Butein-mediated antitumor activities were substantially impaired in Aurora B knockdown cells, suggesting Aurora B was an important target of butein in HCC. Oral administration of butein substantially restrained HCC xenograft growth and the expressions of Ki67 and phosphor-histone H3 were significantly decreased in butein-treated tissue. To the best of our knowledge, our studies revealed that Aurora B was the direct target of butein in HCC.

The transformation of nonmuscle-invasive bladder cancer (BLCa) to muscle-invasive type and distant metastasis are the two major threats to patients after surgery. Thus, it is important to identify the key genes of BLCa cell invasion and metastasis. Long noncoding RNA (lncRNA) is a potential clinical tool for cancer diagnosis and treatment. Herein, we verified that lncRNA SNHG3 is upregulated in human BLCa specimens and is proportional to poor clinical prognosis via a combination of bioinformatic analyses and wet bench experiments. Then, we constructed SNHG3 knockdown and overexpression cell models via lentiviral packaging and CRISPR-Cas9 technique. Fluorescence in situ hybridization assay showed that SNHG3 is distributed in both the nucleus and cytoplasm of BLCa cell lines. In vitro assays including CCK-8, EdU, colony formation, wound healing, transwell, and tube formation demonstrated that SNHG3 knockdown and overexpression potently inhibited and enhanced BLCa cell proliferation, migration, invasion, and angiogenesis. In addition, IVIS imaging revealed that SNHG3 knockdown could significantly inhibit M-NSG mice xenograft tumor growth. Next, RNA sequencing, bioinformatics analyses and western blots indicated that SNHG3 could promote c-MYC expression. RNA immunoprecipitation, actinomycin D assay and western blot assays suggested that SNHG3 could also bind c-MYC protein which subsequently facilitate the stabilization of BMI1 mRNA, thus enhancing BMI1 protein level. However, SNHG3 knockdown had a slightly weaker inhibitory effect on BMI1 expression than c-MYC knockdown. Further, in vitro assays demonstrated that BMI1 knockdown could suppress the SNHG3 activation-induced tumor promoting effect in BLCa cells. Overall, this study has provided new insights into the potential implication of lncRNA SNHG3 in the pathogenesis of BLCa. Importantly, SNHG3/c-MYC/BMI1 axis may be a novel target for regulating tumor growth and metastasis in BLCa patients.

BACKGROUND The C-terminus of E1A binding proteins (CTBPs) has recently been shown to stimulate tumorigenesis in several human tissues by participating in cell signal transduction. However, to date, the expression profile of CTBP isoforms in hepatocellular carcinoma (HCC) and the impact of CTBPs on HCC cell phenotype have not been fully explored. MATERIAL AND METHODS The expression level of CTBP1 was investigated in various HCC cell lines and HCC tissues by RT-qPCR, Western blotting, and immunohistochemistry assays. The phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 was utilized to treat hepatic astrocyte cells, and the impact of CTBP1 on proliferation and metastasis of hepatic astrocytes and HCC cells was accessed by CCK-8, clone-forming, Transwell chamber, and cell scratch assays. RESULTS Increased expression of CTBP1 was observed in HCC tissues and was a predictor of poor prognosis in HCC patients. CTBP1 modified proliferation and migratory activity of HCC cells via the PI3K/protein kinase B (Akt) signaling pathway in hepatic astrocytes. Moreover, genetic loss of CTBP1 significantly reduced the metastatic activity of HCC cells in vitro. CONCLUSIONS Our data suggest that the loss of CTBP1 suppresses cell proliferative and invasive activity of HCC cells via the PI3K/Akt pathway.

Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels.

Hepatic epithelioid angiomyolipoma (EAML) is a rare type of hepatic tumor. Due to a lack of adequate understanding about this tumor, hepatic EAML is often misdiagnosed as other diseases with similar clinical characteristics such as hepatic cancer. In the present study, 3 cases of hepatic EAML are reported, and the main clinicopathological features of this disease are presented, based on a literature search that included articles published in English between February 2000 and September 2014. A total of 24 hepatic EAML cases were considered, of which, 17 were females and 4 presented multiple liver lesions. Among the patients with single lesions, 2 underwent surgery and relapsed after 5 months and 9 years, respectively. Immunohistochemical staining was positive for human melanoma black-45 in the present 3 cases. The aim of the present study was to focus the attention of clinicians on this type of hepatic tumor in order to improve its diagnosis and treatment.

To investigate whether the abscopal effects of cranial irradiation (C-irradiation) cause testicular damage in mice, male C57BL/6 mice (9weeks of age) were randomly divided into a sham irradiation group, a shielded group and a C-irradiation group and administered sham/shielded irradiation or C-irradiation at a dose rate of 2.33Gy/min (5Gy/d for 4 d consecutively). All mice were sacrificed at 4weeks after C-irradiation. We calculated the testis index, observed testicular histology by haematoxylin-eosin (HE) staining and observed testicular ultrastructure by transmission electron microscopy. Western blotting was used to determine the protein levels of Bax, Bcl-2, Cleaved caspase 3, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in the testes of mice. Immunofluorescence staining was performed to detect the expression of Cleaved caspase 3 and 3β hydroxysteroid dehydrogenase (3βHSD), and a TUNEL assay was used to confirm the location of apoptotic cells. The levels of testosterone (T), GDNF and SCF were measured by ELISA. We also evaluated the sperm quality in the cauda epididymides by measuring the sperm count, abnormality, survival rate and apoptosis rate. The results showed that there was no significant difference in testicular histology, ultrastructure or sperm quality between the shielded group and sham group. Compared with the sham/shielded group, the C-irradiation group exhibited a lower testis index and severely damaged testicular histology and ultrastructure at 4weeks after C-irradiation. The levels of apoptosis in the testes increased markedly in the C-irradiation group, especially in spermatogonial stem cells. The levels of serum T and testicular 3βHSD did not obviously differ between the sham group and the C-irradiation group, but the levels of GDNF and SCF in the testes increased in the C-irradiation group, compared with the sham group. In addition, the sperm count and survival rate decreased in the C-irradiation group, while the abnormality and apoptosis rate increased. Under these experimental conditions, the abscopal effects of C-irradiation induced testicular damage with regard to both structure and function and ultimately decreased sperm quality in mice. These findings provide novel insights into prevention and treatment targets for male reproductive damage induced by C-irradiation.

Gibberellins (GAs) participate in controlling various aspects of basic plant growth responses. With the exception of bryophytes, GA signalling in land plants, such as lycophytes, ferns and angiosperms, is mediated via GIBBERELLIN-INSENSITIVE DWARF1 (GID1) and DELLA proteins. To explore whether this GID1-DELLA mechanism is present in pines, we cloned an orthologue (PtGID1) of Arabidopsis AtGID1a and two putative DELLA proteins (PtDPL; PtRGA) from Pinus tabuliformis, a widespread indigenous conifer species in China, and studied their recombinant proteins. PtGID1 shares with AtGID1a the conserved HSL motifs for GA binding and an N-terminal feature that are essential for interaction with DELLA proteins. Indeed, A. thaliana 35S:PtGID1 overexpressors showed a strong GA-hypersensitive phenotype compared to the wild type. Interactions between PtGID1 and PtDELLAs, but also interactions between the conifer-angiosperm counterparts (i.e. between AtGID1 and PtDELLAs and between PtGID1 and AtDELLA), were detected in vivo. This demonstrates that pine has functional GID1-DELLA components. The Δ17-domains within PtDPL and PtRGA were identified as potential interaction sites within PtDELLAs. Our results show that PtGID1 has the ability to interact with DELLA and functions as a GA receptor. Thus, a GA-GID1-DELLA signalling module also operates in evolutionarily ancient conifers.

Plants have a profound capacity to regenerate organs from differentiated somatic tissues, based on which propagating plants in vitro was made possible. Beside its use in biotechnology, in vitro shoot regeneration is also an important system to study de novo organogenesis. Phytohormones and transcription factor WUSCHEL (WUS) play critical roles in this process but whether and how epigenetic modifications are involved is unknown. Here, we report that epigenetic marks of DNA methylation and histone modifications regulate de novo shoot regeneration of Arabidopsis through modulating WUS expression and auxin signaling. First, functional loss of key epigenetic genes-including METHYLTRANSFERASE1 (MET1) encoding for DNA methyltransferase, KRYPTONITE (KYP) for the histone 3 lysine 9 (H3K9) methyltransferase, JMJ14 for the histone 3 lysine 4 (H3K4) demethylase, and HAC1 for the histone acetyltransferase-resulted in altered WUS expression and developmental rates of regenerated shoots in vitro. Second, we showed that regulatory regions of WUS were developmentally regulated by both DNA methylation and histone modifications through bisulfite sequencing and chromatin immunoprecipitation. Third, DNA methylation in the regulatory regions of WUS was lost in the met1 mutant, thus leading to increased WUS expression and its localization. Fourth, we did a genome-wide transcriptional analysis and found out that some of differentially expressed genes between wild type and met1 were involved in signal transduction of the phytohormone auxin. We verified that the increased expression of AUXIN RESPONSE FACTOR3 (ARF3) in met1 indeed was due to DNA demethylation, suggesting DNA methylation regulates de novo shoot regeneration by modulating auxin signaling. We propose that DNA methylation and histone modifications regulate de novo shoot regeneration by modulating WUS expression and auxin signaling. The study demonstrates that, although molecular components involved in organogenesis are divergently evolved in plants and animals, epigenetic modifications play an evolutionarily convergent role in this process.