Search

The E3 ubiquitin ligase HECTD3 is a homologue of the E6-related protein carboxyl terminus, which plays a crucial role in biological processes and tumourigenesis. However, the functional characterisation of HECTD3 in glioblastoma is still elusive.Determination of the functional role of HECTD3 in glioblastoma was made by a combination of HECTD3 molecular pattern analysis from human glioblastoma databases and subcutaneous and in situ injections of tumours in mice models.This study reports that the DOC domain of HECTD3 interacts with the DNA binding domain of PARP1, and HECTD3 mediated the K63-linked polyubiquitination of PARP1 and stabilised the latter expression. Moreover, the Cysteine (Cys) 823 (ubiquitin-binding site) mutation of HECTD3 significantly reduced PARP1 polyubiquitination and HECTD3 was involved in the recruitment of ubiquitin-related molecules to PARP1 ubiquitin-binding sites (Lysines 209 and 221, respectively). Lastly, activation of EGFR-mediated signalling pathways by HECTD3 regulates PARP1 polyubiquitination.Our results unveil the potential role of HECTD3 in glioblastoma and strongly preconise further investigation and consider HECTD3 as a promising therapeutic marker for glioblastoma treatment.

Particle filter algorithms are a very important branch for visual object tracking in the past decades, showing strong robustness to challenging scenarios with partial occlusion and large-scale variations. However, since a large number of particles need to be extracted for the accurate target state estimation, their tracking efficiency typically suffers especially when meeting deep convolutional features, which have been developed for handling significant variations of the target appearance in the visual tracking community. In this paper, we propose to elegantly exploit deep convolutional features with few particles in a novel hierarchical particle filter, which formulates correlation filters as observation models and breaks the standard particle filter framework down into two constituent particle layers, namely, particle translation layer and particle scale layer. The particle translation layer focuses on the object location with the deep convolutional features capturing semantics but failing to precisely estimate the object scale, while the particle scale layer pays attention to large-scale variations with the lightweight hand-crafted features handling spatial details of the object size. Moreover, an efficient ensemble method is proposed to help explore deeper convolutional features with more semantics in the particle translation layer. Extensive experiments on four challenging tracking datasets, including OTB-2013, OTB-2015, VOT2014, and VOT2015 demonstrate that the proposed method performs favorably against a number of state-of-the-art trackers.

In this thesis, a low-power dissipation high-speed double-tail dynamic comparator is designed. Based on the principles of charge-steering, a clock charge pump is used at the tail of the latch stage to replace the clock current source, which reduce the output swing and kick-back noise of the comparator. Meanwhile, digital logic is added to the pre-amplification stage to eliminate quiescent current and further reduce power consumption. Based on the SMIC 28nm CMOS process, the proposed comparator is simulated and verified. The results show that under the condition of 0.9V supply voltage and 1MHz sampling frequency, the power dissipation is 5.4μW, the delay is 245ps, and the offset voltage is 6.9mV. Compared with a high-speed comparator, under the premise of achieving the same performance, the power consumption is reduced by 69%.

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Histone methylation status is an important process associated with cell growth, survival, differentiation and gene expression in human diseases. As a member of the KDM4 family, KDM4B specifically targets H1.4K26, H3K9, H3K36, and H4K20, which affects both histone methylation and gene expression. Therefore, KDM4B is often regarded as a key intermediate protein in cellular pathways that plays an important role in growth and development as well as organ differentiation. However, KDM4B is broadly defined as an oncoprotein that plays key roles in processes related to tumorigenesis, including cell proliferation, cell survival, metastasis and so on. In this review, we discuss the diverse roles of KDM4B in contributing to cancer progression and normal developmental processes. Furthermore, we focus on recent studies highlighting the oncogenic functions of KDM4B in various kinds of cancers, which may be a novel therapeutic target for cancer treatment. We also provide a relatively complete report of the progress of research related to KDM4B inhibitors and discuss their potential as therapeutic agents for overcoming cancer.

The E3 ubiquitin ligase HECTD3 is homologous with the E6 related protein carboxyl terminus, which plays a vital role in biological modification, including immunoreactivity, drug resistance and apoptosis. Current research indicates that HECTD3 promotes the malignant proliferation of multiple tumors and increases drug tolerance. Our study primarily explored the important function and effects of HECTD3 in gastric cancer. Here, we discovered that HECTD3 is abnormally activated in gastric cancer, and the clinical prognosis database suggested that HECTD3 was strongly expressed in gastric cancer. Depletion of HECTD3 restrained the proliferative and clone abilities of cells and induced the apoptosis of gastric cancer cells. Mechanistically, our findings revealed that interaction between HECTD3 and c-MYC, and that the DOC domain of HECTD3 interacted with the CP and bHLHZ domains of c-MYC. Furthermore, we discovered that HECTD3 mediates K29-linked polyubiquitination of c-MYC. Then, our research indicated that cysteine mutation at amino acid 823 (ubiquitinase active site) of HECTD3 reduces the polyubiquitination of c-MYC. Our experimental results reveal that HECTD3 facilitates the malignant proliferation of gastric cancer by mediating K29 site-linked polyubiquitination of c-MYC. HECTD3 might become a curative marker.

CDGSH iron sulfur domain 2 (CISD2) is reported to be highly expressed in several cancers, but the role of it in neuroblastoma has not been identified yet. Here, for the first time, we show that CISD2 is involved in neuroblastoma tumorigenesis and regulates neuroblastoma cell proliferation and differentiation. We found that high CISD2 expression correlated significantly with poor outcome of neuroblastoma patients, as well as advanced neuroblastoma tumor stages. Knockdown of CISD2 greatly repressed neuroblastoma cell proliferation and tumorigenesis both in vitro and in vivo. Further investigation showed that CISD2 deficiency resulted in cell cycle arrest in G1 phase and induced cell differentiation of neuroblastoma. Several Cyclins and Cyclin-Dependent Kinases (CDKs) were down-regulated by CISD2 knockdown, indicating that CISD2 probably regulates cell cycle through those genes. Together, we provide evidence that CISD2 is an indicator for neuroblastoma patients prognosis and is indispensable for neuroblastoma cell proliferation and tumorigenesis; CISD2 deficiency can induce neuroblastoma cell cycle arrest and differentiation. These findings suggest that CISD2 could work as a novel and potential therapeutic target for neuroblastoma treatment.

In a recent study published in Cancer Research, Xia and colleagues reported that, in cancer, constituents in serine–glycine-one-carbon (SGOC) metabolism exhibit enhanced transcriptional activation and are increasingly utilised, which results in more glucose-derived carbon to serine–glycine biosynthesis. The current work identifies an MYCN-dependent metabolic vulnerability and shows a variety of associations between metabolic reprogramming and enhanced sensitivity to metabolic stress, which may lead the way to unlocking new anticancer therapies. Here, we summarised new insights into the role of SGOC metabolism in the progression of neuroblastoma (NB) with highly activated SGOC metabolism.

Additional file 1: Figure S1. (a) Kaplan-Meier analysis of progression-free survival and the log-rank test P values are indicated for the TCGA dataset (TGCA samples-450). (b) Kaplan-Meier analysis of progression-free survival and the log-rank test P values are indicated for the OncoLnc dataset (OncoLnc STAD samples-378). Table S1. Target Sequence for NUCKS. Table S2. The qRT-PCR primers.

MYC-induced nuclear antigen (MINA53) is a JmjC (jumonji C domain)-containing protein, which is highly expressed in many cancers including glioblastoma. We have revealed in our previous report that MINA53 is a poor prognostic indicator for glioblastoma patients, and knockdown of MINA53 could reduce glioblastoma malignancy. In this study, we found that MINA53 knockdown could decrease the DNA replication initiation in glioblastoma cells. Through further investigations, we revealed that MINA53 could regulate the expression of the CDC45-MCM-GINS (CMG) complex genes, which are vital for DNA replication initiation. Knockdown of MINA53 reduced the CMG genes expression and thus induced DNA replication stress and DNA damage. Furthermore, MINA53 knockdown diminished DNA damage response (DDR) by reducing the ATM/ATR-H2AX pathway activity and finally led glioblastoma cells to apoptosis and death. We further applied a genotoxic drug Doxorubicin and found that MINA53 deficiency sensitized glioblastoma cells to Doxorubicin. Our study reveals that MINA53 is involved in DNA replication initiation and DNA damage response, and provides support for MINA53 as a novel and potential therapeutic target for glioblastoma treatment.

Background The cancer-testis specific gene Opa interacting protein 5 (OIP5) is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5. Growth curve, colony formation, and transwell assays were used to analyze cell proliferation and metastasis. Tumorigenicity potential was investigated in orthotopic tumor models, and immunoprecipitation, chromatin immunoprecipitation, and luciferase assays were employed to explore the mechanisms underlying the activation of OIP5 expression by E2F transcription factor 1 (E2F1) to stabilize and maintain E2F1 signaling. Results OIP5 was found to be upregulated in glioblastoma patients and to impair patient survival, and the increased expression of OIP5 was positively correlated with tumor stage. Compared with short hairpin green fluorescent protein cells, cells in which OIP5 was knocked down exhibited significantly reduced proliferation, metastasis, colony formation, and tumorigenicity abilities, whereas OIP5 recovery enhanced these abilities. OIP5 was highly correlated with cell cycle progression but had no obvious effects on apoptosis. Notably, we demonstrated a feedback loop in which E2F1 activates the expression of OIP5 to stabilize and maintain E2F1 signaling and promote the E2F1-regulated gene expression that is required for aggressive tumor biology. Conclusions Collectively, our findings demonstrate that OIP5 promotes glioblastoma progression and metastasis, suggesting that OIP5 is a potential target for anticancer therapy.

Particle-filter-based methods have made significant contributions to achieve robust visual tracking over the past few years. Although these tracking algorithms achieve superior performance, their real-time application has typically been hindered by the high computational burden attributed to the sampling process of the particle filter. In this paper, we propose an innovative lightweight particle filter tracking (LPFT) approach that retains the robust tracking ability of the particle filter while alleviating the time-consuming sampling burden by the correlation filter method with response maps. Specifically, the proposed tracker fully utilizes the location and confidence information of these maps to predict the object, thereby training a more robust correlation filter based on more accurate predictions compared with standard correlation filters. Additionally, in contrast to most particle-filter-based trackers, the LPFT tracker capable of handling large-scale variations can be incorporated into any tracker that requires fast and accurate scale estimation. We propose the generic parallelization framework and implement another version of the LPFT tracker to validate this incorporation. Extensive evaluations on the OTB-2013 and OTB-2015 benchmarks demonstrate that the proposed tracker achieves very competitive performances with state-of-the-art trackers while operating at over 60 frames per second using hand-crafted features.

The Chinese medicine monomer cynaroside (Cy) is a flavonoid glycoside compound that widely exists in plants and has a variety of pharmacological effects, such as its important role in the respiratory system, cardiovascular system and central nervous system. Studies have reported that Cy has varying degrees of anticancer activity in non-small cell lung cancer, cervical cancer, liver cancer, esophageal cancer and other cancers. However, there are no relevant reports about its role in gastric cancer. The MET/AKT/mTOR signaling pathway plays important roles in regulating various biological processes, including cell proliferation, apoptosis, autophagy, invasion and tumorigenesis. In this study, we confirmed that Cy can inhibit the cell growth, migration and invasion and tumorigenesis in gastric cancer. Our finding shows that Cy can block the MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR and P70S6K. Therefore, the MET/AKT/mTOR axis may be an important target for Cy. In summary, Cy has anti-cancer properties and is expected to be a potential drug for the treatment of gastric cancer.

Latest algorithms for automatic neural architecture search perform remarkable but are basically directionless in search space and computational expensive in training of every intermediate architecture. In this paper, we propose a method for efficient architecture search called EENA (Efficient Evolution of Neural Architecture). Due to the elaborately designed mutation and crossover operations, the evolution process can be guided by the information have already been learned. Therefore, less computational effort will be required while the searching and training time can be reduced significantly. On CIFAR-10 classification, EENA using minimal computational resources (0.65 GPU-days) can design highly effective neural architecture which achieves 2.56% test error with 8.47M parameters. Furthermore, the best architecture discovered is also transferable for CIFAR-100., Accepted by ICCV2019 Neural Architects Workshop (ICCVW)

Tubeimoside-1 (TBMS1) is one of the extracts of rhizoma bolbostemmae, which has remarkable anti-cancer function in the treatment of esophagus and gastric cancer in traditional Chinese medicine. However the mechanisms of its anti-cancer function is remain unclear. In this study, we demonstrate that TBMS1 could inhibit cell growth and metastasis in glioblastoma. MET is a member of the receptor tyrosine kinase family, which amplifies frequently in various human cancers. As an important proto-oncogene, multiple inhibitors have been developed for the therapy of cancers. Here, we found TBMS1 could reduce/decrease the protein level of MET via increasing its Ubiquitination degradation. Therefore, TBMS1 is a promising compound for the treatment of glioblastoma and an inhibitor of MET.

SummaryThe histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9) trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation.

As the first member of glycylcycline bacteriostatic agents, tigecycline is approved as a novel expanded-spectrum antibiotic, which is clinically available. However, accumulating evidence indicated that tigecycline was provided with the potential application in cancer therapy. In this paper, tigecycline was shown to exert an anti-proliferative effect on neuroblastoma cell lines. Furthermore, it was found that tigecycline induced G1-phase cell cycle arrest instead of apoptosis by means of Akt pathway inhibition. In neuroblastoma cell lines, the Akt activator insulin-like growth factor-1 (hereafter referred to as IGF-1) reversed tigecycline-induced cell cycle arrest. Besides, tigecycline inhibited colony formation and suppressed neuroblastoma cells xenograft formation and growth. After tigecycline treatment in vivo, the Akt pathway inhibition was confirmed as well. Collectively, our data provided strong evidences that tigecycline inhibited neuroblastoma cells growth and proliferation through the Akt pathway inhibition in vitro and in vivo. In addition, these results were supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment.

The suppressors of cytokine signaling (SOCS) are a family of intracellular molecules. Many members of this family have been reported to be involved in various physiological processes in invertebrates and vertebrates (e.g., developmental process and immune response). The functions of SOCS molecules seem to remain conserved in animals throughout evolutionary history. The members of the SOCS family play vital roles in the physiological processes by regulating the extent and duration of signaling activities of both Janus Kinase-Signal Transducer and Activators of Transcription (JAK-STAT) and epidermal growth factor receptor (EGFR) pathways in vivo. So far, in different insect species, a variable number of SOCS and SOCS box domain-containing proteins have been identified. These proteins are categorized into different types based on their sequence diversification, leading to an alteration in structure and regulatory function. The biological roles of the many SOCS proteins have been established as a negative or positive regulator of the signaling pathways, as mentioned earlier. Here, we discussed the existing knowledge on the SOCS proteins and their involvement in different biological functions in insects, and future perspectives to further elucidate their physiological roles.

Integrins are cell adhesion receptors, which consists of several transmembrane glycoproteins. They are widely distributed on the cell surface and involved in signal transduction pathways. As a heterodimer, each integrin is composed of one α subunit and one β subunit. Integrins are mainly expressed on lepidopteran hemocytes and involved in cell immune response. The full-length cDNA sequence of BmIntegrin β2 was obtained by PCR and RACE, including 2 434 bp. BmIntegrin β2 was predicted to be a transmembrane protein. The BmIntegrin β2 expression profile was detected by qRT-PCR at L4D3 or L5D3 larval stage, and it was highly expressed in hemocyte and hematopoietic organ. Anti-BmIntegrin β2 polyclonal antibody was generated following prokaryotic expression, protein purification and animal immunization, which is highly specific and effective for recognizing BmIntegrin β2 protein through Western blotting. The results of plasmatocytes adhesion experiment showed that BmIntegrin β2 plays an important role on the adhesion and spreading of plasmatocytes to foreign surfaces. This study provides a foundation for further research of the biological function of BmIntegrin β2 gene.整合素是一类广泛分布于细胞表面的黏附分子受体，是由α 和β 两个亚基组成的异源二聚体跨膜蛋白，其是细胞内外信号转导的中间桥梁。在鳞翅目昆虫细胞内，整合素主要表达于血细胞，参与昆虫细胞免疫反应进程。文中首先通过RACE 技术等，克隆获得BmIntegrin β2 基因cDNA 全长序列2 434 bp；并对其蛋白结构域进行了预测，主要包括信号肽、一段较大的胞外域，单次跨膜结构和较短的胞内域；利用qRT-PCR 技术检测了家蚕4 龄3 天和5 龄3 天的BmIntegrin β2 各组织表达图谱，结果显示其主要在血细胞和造血器官中高表达；然后再经原核诱导表达、蛋白纯化及免疫动物后获得BmIntegrin β2 抗体。通过对BmIntegrin β2 蛋白功能作用的研究发现，BmIntegrin β2 抗体可显著地减少浆细胞的数量，这从侧面说明BmIntegrin β2 抗体可能抑制了浆细胞的延伸性和粘附能力。该结果不仅为BmIntegrin β2 参与家蚕细胞的免疫反应奠定了基础，还提供了一个新的研究视野。.

Sirtuin family members are characterized by either mono-ADP-ribosyltransferase or deacylase activity and are linked to various cancer-related biological pathways as regulators of transcriptional progression. Sirtuins play fundamental roles in carcinogenesis and maintenance of the malignant phenotype, mainly participating in cancer cell viability, apoptosis, metastasis, and tumorigenesis. Although sirtuin family members have a high degree of homology, they may play different roles in various kinds of cancer. This review highlights their fundamental roles in tumorigenesis and cancer development and provides a critical discussion of their dual roles in cancer, namely, as tumor promoters or tumor suppressors.

Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD+ dependent protein modifying enzymes, sirtuins (SIRT1-SIRT7) have multiple catalytic functions such as deacetylase, desuccinylase, demalonylase, demyristoylase, depalmitoylase, and/or mono-ADP-ribosyltransferase. They play important roles in regulating cell metabolism, especially in glucose and lipid metabolism, thereby exerting complex functions in either increasing or decreasing malignant characteristics in tumors. This review highlights the major function and its mechanisms of sirtuins in cellular metabolic reprogramming, such as glucose metabolism including aerobic glycolysis (the Warburg effect), oxidative phosphorylation (OXPHOS)/tricarboxylic acid (TCA) cycle and glutamine metabolism; lipometabolism including fatty acid metabolism, cholesterol metabolism, ketone body metabolism and acetate metabolism; as well as leucine metabolism and the urea cycle in tumorigenesis and cancer development.

Tingting Wu,1–4 Hongjuan Cui,5 Yamei Xu,1–4 Quangao Du,1–4 Erhu Zhao,5 Jiangjun Cao,5 Ling Nie,1–4 Gang Fu,1–4 Aishu Ren1–3,6 1College of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Oral Implantology, Stomatological Hospital of Chongqing Medical University,Chongqing, People’s Republic of China; 5State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, People’s Republic of China; 6Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from traditional Chinese medicine tubeimoside, exerts a cytotoxic effect on several human cancer cell lines. However, no study has focused on whether TBMS1 works on oral squamous cell carcinoma (OSCC). Materials and methods: We treated OSCC cells with TBMS1 to detect the effect and relevant molecular basis of TBMS1 for the first time. We chose two oral cancer cell lines, CAL27 and SCC15, for this study. First, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide assay and cell proliferation5'-bromo-2'-deoxyuridine assay were carried out to detect cell growth. Second, colony formation assay was performed to assess clonogenesis capacity. Next apoptosis was analyzed by flow cytometry. Subsequently, wound healing and transwell assays were applied to explore cell migration. Finally, Western blot was further performed to examine corresponding proteins’ expression change. Results: Our data showed that TBMS1 significantly suppressed proliferation of OSCC cells in a dose- and time-dependent manner and it inhibited migration of OSCC cells as well. After treatment with TBMS1, OSCC cells underwent cell apoptosis. Furthermore, Western blot demonstrated that TBMS1 downregulated apoptosis-associated proteins such as PARP, p-ERK1/2, Bcl-2, caspase-3, caspase-7 and caspase-8 and upregulated cleaved PARP, cleaved caspase-3 and cleaved caspase-9. It could also reduce expression of c-Myc and MMP-7. Meanwhile, TBMS1 did not change the total ERK1/2 expression. Conclusion: These results revealed that TBMS1 might be a potential chemotherapeutic drug for the management of OSCC. Keywords: tubeimoside-1, chemotherapeutic drug, oral squamous cell carcinoma, OSCC, apoptosis, underlying mechanism

Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells. MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in multiple human cancers. MCL1 is also known as a potential contributor for the resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1 is, therefore, regarded as a potential target for cancer therapy. Here, for the first time, we unveil that demethylzeylasteral suppresses the expression of MCL1. Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby inhibits it’s ubiquitin-dependent degradation. Together, demethylzeylasteral is a promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a potential inhibitor of MCL1.

Mitochondrial DNA (mtDNA) D-loop sequences of 666 individuals (including 109 new individuals, 557 individuals retrieved from GenBank) from 33 Chinese domestic goat breeds throughout China were used to investigate their mtDNA variability and molecular phylogeography. The results showed that all goat breeds in this study proved to be extremely diverse, and the average haplotype diversity and nucleotide diversity were 0.990 ± 0.001 and 0.032 ± 0.001, respectively. The 666 sequences gave 326 different haplotypes. Phylogenetic analyses revealed that there were 4 mtDNA haplogroups identified in Chinese domestic goats, in which haplogroup A was predominant and widely distributed. Our finding was consistent with archaeological data and other genetic diversity studies. Amova analysis showed there was significant geographical structuring. Almost 84.31 % of genetic variation was included in the within-breed variance component and only 4.69 % was observed among the geographic distributions. This genetic diversity results further supported the previous view of multiple maternal origins of Chinese domestic goats, and the results on the phylogenetic relationship contributed to a better understanding of the history of goat domestication and modern production of domestic goats.

Gastric cancer is difficult to cure due to its clinical heterogeneity and the complexity of its molecular mechanisms. KDM2B, a member of the JHDM family, functions as a histone lysine demethylase. However, the role and mechanisms of KDM2B in gastric cancer have not been elucidated. Here, we showed that KDM2B is commonly expressed in gastric cancer cells. The downregulation of KDM2B immediately induces autophagy, followed by the inhibition of proliferation. The compound 3-methyladenine (3-MA), an inhibitor of autophagy, largely rescues autophagy and the inhibition of cell proliferation induced by KDM2B knockdown. In this process, we observed a downregulation of the phosphorylation of Akt and its downstream effectors mTOR and p70S6K and an upregulation of Erk phosphorylation after KDM2B knockdown. In a xenograft model, the downregulation of KDM2B can inhibit tumour growth. The conversion of LC3-I to LC3-II also decreased concomitantly in vivo, which is a hallmark of autophagy. Taken together, our study was the first to demonstrate a novel regulatory role of KDM2B in autophagy and cell growth in gastric cancer cells. Our findings suggest that KDM2B may serve as a novel therapeutic target for gastric cancer therapy.