Wenyi Gu - Academia.edu (original) (raw)

Papers by Wenyi Gu

Background: Previous studies reported that emodin extracted from Rheum palmatum L. exerts antipro... more Background: Previous studies reported that emodin extracted from Rheum palmatum L. exerts antiproliferation and antimetastatic effects in a variety of human cancer types. However, the role of emodin in hepatocellular carcinoma (HCC) remain unknown.Methods: EdU and colony formation assays were performed to evaluate the effects of emodin on proliferation. The mobility capacities of HCC treated with emodin were evaluated using wound healing assay. Transwell invasion and migration assays were performed to evaluate anti-migratory and anti-invasive effects of emodin on HCC. Annexin V-FITC/PI was performed to analyze the apoptosis. PI stain was performed to analyze cell cycle. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) induced by emodin in HCC. The impact of emodin on autophagic flux in HepG2 cells was examined by mCherry-GFP-LC3 analysis. Western blot was used to assess the protein expressions of epithelial-mesenchymal transition (EMT), autoph...

Scientific Reports, 2017

We sequenced the mitochondrial (mt) genome of the grass thrips, Anaphothrips obscurus, which is h... more We sequenced the mitochondrial (mt) genome of the grass thrips, Anaphothrips obscurus, which is highly rearranged and differs from the four thrips species reported previously in the arrangement of both tRNA genes and a protein-coding gene, nad3, and in the copy number of the control region (CR). We reconstructed the phylogeny of the thrips with mt genome sequences, and used it as a framework to gain insights into mt genome evolution in thrips. It is evident that A. obscurus is less rearranged in mt genome organization than the other four known thrips. nad3 is in its ancestral location in A. obscurus but was translocated in other four thrips. Also, A. obscurus has one CR, which is ancestral to hexapods whereas other thrips have two or three CRs. All of the five thrips whose mt genomes have been sequenced to date are from the subfamily Thripinae, which represents about a quarter of the species richness in the order Thysanoptera. The high variation in mt genome organization observed in...

PloS one, 2017

The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithe... more The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithelial transition [MET]) have been shown to be associated with tumor cell invasion and metastasis in different carcinomas. The EMT and MET have recently been shown to play a key role in the pathogenic processes of sarcomas, which are completely different from those of carcinomas. However, the definitive roles of the EMT in the tumorigenesis of synovial sarcomas remain unknown. Here, we explored whether transforming growth factor (TGF)-β signaling, an important oncogenic event in synovial sarcoma, modulates tumor cell characteristics related to the EMT, such as cell adhesion, migration, invasion, and proliferation. Interestingly, we found that TGF-β1 induced tumor cell activation, resulting in a tendency to aggregate and biphasic-like features. TGF-β1 also caused downregulation of E-cadherin and subsequent upregulation of N-cadherin, Snail, and Slug, which are responsible for EMT-like pheno...

Calcified tissue international, Jul 1, 2016

This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone i... more This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone sample set. I...

RSC Advances, 2013

The enrichment of peptides is a key technique in mass spectrometry based proteomics and peptidomi... more The enrichment of peptides is a key technique in mass spectrometry based proteomics and peptidomics. The tailored design of mesoporous materials with an optimum pore size for highly-efficient enrichment of target molecules is a challenging issue. Herein, a series of periodic mesoporous organosilicas (PMOs) are synthesized with the same structural symmetry (p6mm) and similar morphology, while the pore sizes are finely adjusted from 2.6 to 7.3 nm. Their enrichment performance for a standard E7 peptide (molecular weight 1120.6 Da) is investigated via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). It is found that PMO with the mesopore size of 5.8 nm exhibits the highest enrichment performance towards the E7 peptide. Moreover, a block copolymer (Brij 78) with the similar molecular weight (1150.8 Da) to E7 is also used to further study the influence of mesopore size upon the enrichment efficiency. It is shown that PMO with the pore size of 5.8 nm still holds the best enriching ability towards Brij 78 at low concentrations. The adsorption capacity of the PMOs for Brij 78 are further studied at high concentrations, showing a dependence on both the pore volume and pore size. This research may shed light on advanced enrichment and analysis of various peptides and polymers using designed nanoporous materials, an important topic in both material and biological science.

Frontiers in Bioscience, 2013

Diseases of the Esophagus, 2013

Aberrant DNA methylation of promoter region CpG islands may serve as an alternative mechanism to ... more Aberrant DNA methylation of promoter region CpG islands may serve as an alternative mechanism to genetic defects in the inactivation of tumor suppressor genes (TSGs) in human malignancies. The aim of this study was to examine the promoter methylation status of the PTEN TSG and its association with esophageal squamous cell carcinoma (ESCC) carcinogenesis in a Chinese Kazakh population, which is known to have a relatively high ESCC incidence and mortality. The methylation status of the PTEN promoter region was determined in patients with ESCC (n = 95) and healthy individuals (n = 65) using highly sensitive Sequenom Epityper assays. The methylation level of the PTEN gene was significantly higher in patients with ESCC than in healthy controls. The median methylation level was 10.0% (interquartile range [IQR]: 7.0-11.0%) in patients with ESCC and 6.0% in controls (IQR: 4.0-9.0%; P = 0.001). PTEN methylation levels were higher in male patients with ESCC than in male controls, whereas a trend toward significance was observed between female patients with ESCC and female controls (P = 0.005 and P = 0.086, respectively). The PTEN methylation level was associated with histopathological grade and lymph node metastasis in patients with ESCC (P = 0.002 and P = 0.009, respectively). To our knowledge, this is the first report to show the presence of PTEN promoter CpG hypermethylation in ESCC and its association with tumor metastasis.

Arthritis Research & Therapy, 2013

Journal of Translational Medicine

Background Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and... more Background Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. Methods In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. Results In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-β1 which activated the TGFβR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFβ signaling inhibitor SB431542 or knockdown of TGFβR1 could reverse ...

Cancers

Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thu... more Cancer stem cells (CSCs) are primarily responsible for tumour drug resistance and metastasis; thus, targeting CSCs can be a promising approach to stop cancer recurrence. However, CSCs are small in numbers and readily differentiate into matured cancer cells, making the study of their biological features, including therapeutic targets, difficult. The use of three-dimensional (3D) culture systems to enrich CSCs has some limitations, including low sphere forming efficiency, enzymatic digestion that may damage surface proteins, and more importantly no means to sustain the stem properties. A responsive 3D polymer extracellular matrix (ECM) system coated with RGD was used to enrich CSCs, sustain stemness and avoid enzymatic dissociation. RGD was used as a targeting motif and a ligand to bind integrin receptors. We found that the system was able to increase sphere forming efficiency, promote the growth of spheric cells, and maintain stemness-associated properties compared to the current 3D ...

Pharmaceutics

To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chem... more To overcome the severe side effects of cancer chemotherapy, it is vital to develop targeting chemotherapeutic delivery systems with the potent inhibition of tumour growth, angiogenesis, invasion and migration at low drug dosages. For this purpose, we co-loaded a conventional antiworm drug, albendazole (ABZ), and a TOPK inhibitor, OTS964, into lipid-coated calcium phosphate (LCP) nanoparticles for skin cancer treatment. OTS- and ABZ-loaded LCP (OTS-ABZ-LCP) showed a synergistic cytotoxicity against skin cancer cells through their specific cancerous pathways, without obvious toxicity to healthy cell lines. Moreover, dual-targeting the programmed death ligand-1 (PD-L1) and folate receptor overexpressed on the surface of skin cancer cells completely suppressed the skin tumour growth at low doses of ABZ and OTS. In summary, ABZ and OTS co-loaded dual-targeting LCP NPs represent a promising platform with high potentials against complicated cancers where PD-L1/FA dual targeting appears as ...

PeerJ

Background We aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the ma... more Background We aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the malignant behaviors of SH-SY5Y cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). Methods The KSHV-infected (SK-RG) and uninfected SH-SY5Y parent cells were compared for differentially expressed miRNAs using transcriptome sequencing. Then miR-34a-5p was upregulated in SK-RG cells by the miRNA mimics transfection. Cell proliferation ability was determined by MTT and plate clone assays. The cell cycle was assessed by flow cytometry analysis, and CDK4, CDK6, cyclin D1 levels were determined by Western blot analysis. The migration behavior was detected by wound healing and transwell assays. The protein levels of MMP2 and MMP9 were measured by Western blot analysis. The regulation of c-fos by miR-34a-5p was detected by the dual-luciferase reporter gene assay. Rescue assays were carried out by upregulating c-fos in miR-34a-5p-overexpressing SK-RG cells. KSHV DNA copy numbers and...

Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded ... more Effective inhibition of colon cancer cell growth with MgAl-layered double hydroxide (LDH) loaded 5-FU and PI3K/mTOR dual inhibitor BEZ-235 through apoptotic pathways

International journal of clinical and experimental pathology, 2018

Polo-like kinase1 (PLK1) is a new therapeutic target for osteosarcoma with good application prosp... more Polo-like kinase1 (PLK1) is a new therapeutic target for osteosarcoma with good application prospects. Whether PLK1 is highly expressed in chondrosarcoma and whether PLK1 can be a potential therapeutic target for chondrosarcoma are worth exploring. However, PLK1 expression in chondrosarcoma is scarcely investigated. Therefore, we collected 11 cases of chondrosarcoma and 26 cases of osteochondroma with complete clinical pathological data and used immunohistochemical staining to detect the expression of PLK1 in chondrosarcoma and osteochondroma and then studied its significance and relationship with clinical pathological parameters. Our results showed that the positive expression rate of PLK1 in chondrosarcoma tissue (90.91%, 10/11) was significantly higher than the rate of osteochondroma tissues (53.85%, 14/26) (P<0.05). The expression of PLK1 enhanced gradually with the increase in histological grade (P<0.05). PLK1 was highly expressed in chondrosarcoma, and the high expressio...

Frontiers in Nanotechnology, 2021

Benzimidazole (BMZ) family of anti-worm drugs has been now repurposed as anti-cancer drugs. Howev... more Benzimidazole (BMZ) family of anti-worm drugs has been now repurposed as anti-cancer drugs. However, offering a general reformulation method for these drugs is essential due to their hydrophobicity and low aqueous solubility. In this work, we developed a general approach to load typical BMZ drugs as tiny nanocrystals within lipid-coated calcium phosphate (LCP) nanoparticles. BMZ drug-loaded LCP nanoparticles increased their solubility in PBS by 100–200% and significantly enhanced the anti-cancer efficacy in the treatment of B16F0 melanoma cells. These drug-LCP nanoparticles induced much more cancer cell apoptosis, generated much more reactive oxygen species (ROS) and inhibited Bcl-2 expression of cancer cells. Moreover, BMZ drug-loaded LCP nanoparticles caused morphological change and extension disruption of cancer cells, and significantly reduced migration activity, representing high possibility for inhibition of tumor dissemination and metastasis. Very advantageously, BMZ drug-loa...

Nanomaterials, 2019

Suitable carriers are crucial to RNAi applications for cancer genotherapy and T-cell immunotherap... more Suitable carriers are crucial to RNAi applications for cancer genotherapy and T-cell immunotherapy. In this research, we selected two extensively-investigated biocompatible inorganic nanoparticle carriers, i.e., layered double hydroxide (LDH) and lipid-coated calcium phosphate (LCP) and then compared their efficacy for siRNA delivery in T cells, in order to understand which carrier is more efficient in delivering functional programmed cell death protein 1 siRNA (PD-1 siRNA) to suspended T lymphocytes. Both LDH and LCP nanoparticles quickly delivered gene segment to mouse T cell lines (EL4), while the LCP nanoparticles exhibited more cellular uptake and higher PD-1 gene silence efficiency. We further demonstrated that LCP nanoparticles successfully reduced the expression of PD-1 in human ex vivo tumor infiltrating lymphocytes (TILs). Thus, LCP nanoparticles can be used as a better nano-carrier for gene therapy in lymphocytes, especially in regards to TIL-related cancer immunotherapy.

BMC Cancer, 2019

Background: Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expr... more Background: Programmed cell death ligand 1 (PD-L1) is an important immune-inhibitory protein expressed on cancer cells to mediate cancer escape through interaction with PD-1 expressed on activated T lymphocytes (T cells). Previously, we reported that colon and breast cancer stem cells (CSCs) expressed much higher levels of PD-L1 than their parental cells, suggesting they will be more resistant to immune attack. Methods: We investigated the underlining mechanism of PD-L1 increase in colon CSCs, with a special focus on the effect of insulin and epithelial growth factor (EGF), the two fundamental components to sustain the metabolism and stemness in the culture of CSCs. Results: We found that insulin increased the total and surface PD-L1 levels through PI3K/Akt/mTOR pathway as the increase could be inhibited by the dual inhibitor of the pathway, BEZ235. EGF didn't affect the total PD-L1 levels of CSCs but increased the cell surface protein levels by flow cytometry analysis, indicating EGF promotes the transport of PD-L1 to the cell surface. Blocking cell surface PD-L1 with a specific antibody resulted in a significant reduction of tumour sphere formation but didn't interfere with the sphere growth, suggesting that cell surface PD-L1 may act as an adhering molecule for CSCs. Conclusions: Apart from the essential roles in metabolism and stemness, insulin and EGF involve in up-regulation of PD-L1 expression in colon CSCs, therefore the inhibition of insulin and EGF/EGFR pathways can be considered for cancer immunotherapy or combined with PD-1/PD-L1 antibody-based cancer immunotherapy to eliminate CSCs.