Protein regulator of cytokinesis 1 accentuates cholangiocarcinoma progression via mTORC1-mediated glycolysis.

This study aimed to investigate the expression of protein regulator of cytokinesis 1 (PRC1) in cholangiocarcinoma (CHOL) and elucidate its potential impact as well as the underlying mechanisms governing the progression of CHOL. In this study, we used CHOL cells (HUCCT1, RBE, and CCLP1) and conducted a series of experiments, including qRT-PCR, cell counting kit-8 assays, EdU assays, flow cytometry, wound healing assays, Transwell assays, western blotting, double luciferase assays, and ELISA. Subsequently, a mouse model was established using cancer cell injections. Haematoxylin-eosin staining, along with Ki67 and TUNEL assays, were employed to assess tissue histopathology, cell proliferation, and apoptosis. Our findings revealed significantly elevated PRC1 expression in CHOL. According to bioinformatics analysis, it was found that the increased PRC1 level is correlated with the high tumour grades, metastases, and unfavourable prognoses. Notably, PRC1 knockdown inhibited cell viability, proliferation, migration, and invasion while promoting apoptosis in CHOL cells. Analysing TCGA-CHOL data and utilising transcription factor prediction tools (hTFtarget and HumanTFDB), we identified that genes positively correlated with PRC1 in TCGA-CHOL intersect with predicted transcription factors, revealing the activation of PRC1 by forkhead box protein M1 (FOXM1). Moreover, PRC1 was found to exert regulatory control over glycolysis and the mammalian target of rapamycin complex 1 (mTORC1) pathway in the context of CHOL based on KEGG and GSEA analysis. Collectively, these results underscore the pivotal role of PRC1 in CHOL progression, wherein it modulates glycolysis and the mTORC1 pathway under the regulatory influence of FOXM1.

Key Modulation of ROS and HSP for Effective Therapy Against Hypoxic Tumor with Multifunctional Nanosystem.

Background: Though nanomedicine-based photothermal therapy (PTT) has demonstrated promising prospect in tumor treatment due to its high therapeutic efficiency and controllable range, the overexpression of heat shock proteins (HSPs) during PTT can lead to intracellular thermal resistance and reduce its effectiveness. Reactive oxygen species (ROS), followed by the application of chemodynamic therapy (CDT) and photodynamic therapy (PDT), can eliminate HSPs and overcome thermal resistance. However, the tumor microenvironment, including hypoxia and glutathione (GSH) overexpression, impedes the production of ROS and therapeutic efficacy of CDT and PDT. Therefore, we proposed a multifunctional nanoplatform (HMPB@TCPP-Cu) driving PTT/ PDT/ CDT synergistic therapy for tumor treatment via modulating ROS and HSPs. Methods and Results: In this work, a novel nanoplatform (HMPB@TCPP-Cu) composed of O2/PTT supplier HMPB (hollow mesoporous Prussian blue) and the loaded PDT/CDT agent (TCPP-Cu2+) was prepared. HMPB acts as an photothermal converter, effectively raising the tumor temperature and inducing apoptosis. HMPB is also a potent catalase-like nanozyme, which can catalyze hydrogen peroxide into oxygen and reduce tumor hypoxia, thus elevating the efficiency of ROS production and the effectiveness of PDT with the wing of sonosensitizer-TCPP. The intracellular glutathione(GSH) was depleted by Cu2+ and •OH was generated along with the Cu2+/Cu+ converting and Cu+-mediated Fenton-like reaction. Subsequently, the increased levels of ROS effectively eliminate intratumoral thermal resistance. The HMPB@TCPP-Cu has achieved synergistic PTT/PDT/CDT for hepatoblastoma treatment and significant inhibition of tumor growth was detected both in vitro and in vivo. Conclusion: This study presents a multifunctional nanoplatform that combines photothermal/ chemodynamic/ photodynamic therapy for efficient hepatoblastoma treatment via modulating ROS and HSPs. Collectively, this study provides an appealing strategy in the cleavage of thermal resistance and a novel assistance and enhancement on thermal-related therapies.

Spatially resolved visualization of reprogrammed metabolism in hepatocellular carcinoma by mass spectrometry imaging.

BACKGROUND: Metabolic reprogramming refers to tumor-associated metabolic alterations during tumorigenesis and has been regarded as one of the most important features of cancer. Profiling the altered metabolites and lipids in hepatocellular carcinoma with spatial signature will not only enhance our understanding of tumor metabolic reprogramming, but also offer potential metabolic liabilities that might be exploited for hepatocellular carcinoma therapy. METHODS: We perform matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) analysis on both hepatocellular carcinoma xenograft mouse model and hepatocellular carcinoma patients. Discriminatory metabolites that altered during the development of hepatocellular carcinoma are screened and imaged in xenograft mouse model and are further validated in 21 hepatocellular carcinoma patients. RESULTS: We discover stepwise metabolic alterations and progressively increasing metabolic heterogeneity during the growth of hepatocellular carcinoma. Arginine and its metabolites spermine and spermidine, choline and phosphatidylcholine metabolism, and fatty acids were found to be significantly reprogrammed in hepatocellular carcinoma tissues. CONCLUSIONS: The spatially resolved profiling of the metabolites and lipids in highly heterogeneous hepatocellular carcinoma tissue will contribute to obtaining precise metabolic information for the understanding of tumor metabolic reprogramming.

Moscatilin suppresses the inflammation from macrophages and T cells.

In this study, we aim to investigate moscatilin in alleviating symptoms of autoimmune liver disease (ALD) in a concanavalin A (ConA)-induced liver injury mouse model and elucidate the underlying mechanisms. ALD mouse models were constructed by intravenous injection of ConA (20 mg/kg) and the serum level of alanine aminotransferase (ALT) was measured using an enzyme-linked immunosorbent assay. Moscatilin in various doses was administered for two days starting from a day before the ConA injection. We showed that moscatilin dose-dependently decreased ALT levels in liver tissue of ALD mouse models. Ifng and Tnfa also showed significant downregulation in liver tissues. Macrophages only showed significant Tnfa downregulation and CD4+ T cells only showed significant Ifng downregulation at high moscatilin doses. In vivo administration of moscatilin induced interleukin-37 upregulation in hepatic tissues. In vitro, moscatilin also induced IL-37 upregulation in hepatic stellate cell line JS-1 rather than immune cells represented by RAW264.7 and CTLL-2 cell lines, suggesting that the hepatic stellate cell is majorly responsive to moscatilin treatment in terms of interleukin (IL)-37 upregulation. Our data indicate that moscatilin could alleviate liver injury in ConA-induced ALD mouse models through anti-inflammatory activities, warranting further development of moscatilin as a new drug in treating ALD.

Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway.

[This retracts the article DOI: 10.3892/ol.2019.10902.].

Long non-coding RNA LINC00511 regulates the expression of microRNA-625-5p and activates signal transducers and activators of transcription 3 (STAT3) to accelerate the progression of gastric cancer.

This study aimed to investigate the expression, biological function, and downstream mechanism of LINC00511 in gastric cancer (GC). In paired GC samples, LINC00511, miR-625-5p and STAT3 mRNA expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR); STAT3 protein expression was detected by immunohistochemical (IHC). The gain-of-function and loss-of-function models were established, and the proliferative and migrative ability of GC cells were measured by CCK-8 and transwell assays, respectively. The regulatory relationship between miR-625-5p and LINC00511 or STAT3 was examined by bioinformatics analysis, luciferase reporter gene assay, qRT-PCR, and western blot. We reported that LINC00511 and STAT3 expressions in GC tissues and cell lines were observably up-regulated, while miR-625-5p expression was inhibited. High expression of LINC00511 could facilitate the proliferation and promote the migration of GC cells. miR-625-5p was proved to be a downstream target of LINC00511, and LINC00511 could induce the expression of STAT3 by inhibiting the expression of miR-625-5p. Additionally, knockdown of LINC00511 suppressed the growth and lung metastases of CRC cells in nude mice. In conclusion, LINC00511 promotes the GC cell proliferation and migration via targeting the miR-625-5p/STAT3 axis, implying that LINC00511 can function as a target for GC therapy.

[Corrigendum] Novel crosstalk between KLF4 and ZEB1 regulates gemcitabine resistance in pancreatic ductal adenocarcinoma.

Subsequently to the publication of the above article, an interested reader drew to the attention of the Editorial Office that, in Fig. 1C on p. 1242, the flow cytometric images contained what appeared to be regular and repeating groups of cells. The office consequently asked the authors to provide the raw data for these images, as they would have been generated from the printouts, and the authors were able to demonstrate that these apparent anomalies were not contained in the original data. It is possible that the anomalous appearance of the data in this Figure may have resulted either from low resolution of the images, or the Figure itself may have been compressed. We are reprinting Fig. 1C opposite, highlighting the data of interest in greater detail. We trust that this satisfies the concerns of the reader in this instance, and thank them for their enquiry to the Editorial Office. The authors also requested that, after having provided the raw data of the original image in order to clarify the concerns of the reader, they may republish Fig. 1 featuring alternative data for Fig. 1C. The revised version of Fig. 1 is consequently shown on the next page. In this figure, flow cytometric analysis demonstrated that treatment with 10 µM gemcitabine induced the death of 66.5% of the BxPC­3 cells, 29.54% of the Panc­1 cells, and 34.52% of the MIApaca­2 cells (Fig. 1C). The authors confirm that these data support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologise to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 51: 1239­1248, 2017; DOI: 10.3892/ijo.2017.4099].

LncRNA LINC01134 Contributes to Radioresistance in Hepatocellular Carcinoma by Regulating DNA Damage Response via MAPK Signaling Pathway.

Hepatocellular carcinoma (HCC) is a highly mortal cancer that could be treated by radiotherapy. DNA damage response (DDR) is a vital factor affecting cancer development after radiotherapy. Long non-coding RNAs (lncRNAs) have been revealed to regulate DNA damage response and repair in cancer cells. Nevertheless, the function of long intergenic non-protein coding RNA 1134 (LINC01134) has not been explored in DDR. In this study, we targeted digging into the function of LINC01134 in DDR and exploring the underlying mechanism in HCC cells. RT-qPCR was employed to measure LINC01134 expression, and we found LINC01134 was significantly upregulated in HCC cells. Functional analysis suggested that LINC01134 depletion attenuated radioresistance of HCC cells by facilitating DNA damage. In vivo assays demonstrated LINC01134 depletion hindered HCC tumor growth. Mechanism assays unveiled LINC01134 sequestered microRNA-342-3p (miR-342-3p) and recruited insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) protein to modulate mitogen-activated protein kinase 1 (MAPK1) expression, consequently activating MAPK signaling pathway. Rescue assays validated the LINC01134/miR-342-3p/MAPK1 axis in the radio-resistant HCC cells. In conclusion, LINC01134 might be identified to be a useful biomarker for the therapy of HCC.

Serum myonectin is increased after laparoscopic sleeve gastrectomy.

OBJECTIVE: Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating levels of free fatty acids in mice. Recent studies showed that serum myonectin concentration is negatively correlated with obesity. This study was undertaken to evaluate the change of serum myonectin in obese patients after laparoscopic sleeve gastrectomy. METHODS: This study was performed in a population of 42 obese and 58 control subjects from April of 2018 to December of 2019. All obese subjects underwent laparoscopic sleeve gastrectomy. Anthropometric measurements, lipid profiles, HbA1c and serum myonectin were assessed at baseline and six months after laparoscopic sleeve gastrectomy. RESULTS: Serum myonectin concentrations were significantly lower in the obese patients than in the controls. Serum myonectin concentrations were increased at six months after laparoscopic sleeve gastrectomy. Simple linear regression analysis indicated that serum myonectin was negatively correlated with weight, waist circumference, hip circumference, body mass index, fasting plasma glucose, homeostasis model assessment of insulin resistance and HbA1c. Only body mass index was still inversely correlated with serum myonectin after multiple linear regression analysis. CONCLUSION: Serum myonectin is correlated with obesity and increased after laparoscopic sleeve gastrectomy.

Molecular interplay between linc01134 and YY1 dictates hepatocellular carcinoma progression.

BACKGROUND: Revealing the mechanical role of long non-coding RNAs (lncRNAs) in tumorigenesis can contribute to novel therapeutic target for cancers. The regulatory role of linc01134 in hepatocellular carcinoma (HCC) has not been studied yet. MATERIALS AND METHODS: qRT-PCR and western blot were conducted to measure relevant RNA and protein expressions. CCK-8, colony formation, EdU, flow cytometry, wound-healing, transwell assays and xenograft experiments were performed to determine the role of linc01134 in HCC. ChIP and luciferase reporter assays were performed to analyze the effects of Yin Yang-1 (YY1) on linc01134 transcription activity. Relevant mechanical experiments were performed to verify interaction between relative genes. RESULTS: YY1 enhanced linc01134 transcription by interacting with linc01134 promoter. Knockdown of linc01134 inhibited proliferation, migration and epithelial-mesenchymal transition (EMT), yet promoting apoptosis in HCC cells. Mechanically, linc01134 acted as miR-324-5p sponge and interacted with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to increase the stability of YY1 mRNA expression. Up-regulated YY1 continuously stimulated linc01134 expression by enhancing linc01134 promoter activity, forming a positive feedback loop. CONCLUSION: Linc01134/miR-324-5p/IGF2BP1/YY1 feedback loop mediates HCC progression, which possibly provide prognosis and treatment target of HCC.

miR-4510 acts as a tumor suppressor in gastrointestinal stromal tumor by targeting APOC2.

Dysregulation of microRNAs (miRNAs) expression has been demonstrated in gastrointestinal stromal tumor (GIST). In this study, we aimed to determine the differential miRNAs expression in GISTs and explore the functional mechanism of differential miRNAs in GIST cells. We measured differential miRNAs in six pairs of GIST tissues and matched adjacent tissues through a high-throughput sequencing, which was confirmed in 64 pairs of GIST tissues and adjacent tissues by real-time polymerase chain reaction. We found that miR-4510 expression was significantly downregulated in GIST tissues compared to matched control tissues. Luciferase reporter assay identified apolipoprotein C-II (APOC2) as a direct target of miR-4510. Overexpression of miR-4510 inhibited the mRNA and protein expression of APOC2. In addition, overexpression of miR-4510 suppressed GIST cell proliferation, migration, and invasion. Overexpression of miR-4510 also inhibited the phosphorylation of AKT and ERK1/2, reduced the expression of matrix metallopeptidase 2 (MMP2) and MMP9. APOC2 knockdown mimicked the effect of miR-4510 overexpression. Further investigation confirmed that APOC2 was notably upregulated in GIST tissues compared to adjacent control tissues. These results suggested that miR-4510 downregulation could promote GIST progression, including growth, invasion, and metastasis, through increasing APOC2 expression.

Acetyl-11-keto-ß-boswellic acid triggers premature senescence via induction of DNA damage accompanied by impairment of DNA repair genes in hepatocellular carcinoma cells in vitro and in vivo.

Cellular senescence, a state of irreversible growth arrest, occurs in all somatic cells and causes the cells to exhaust replicative capacity. Recently, cellular senescence has been emerging as one of the principal mechanisms of tumor suppression, which can be induced by low doses of therapeutic drugs in cancer cells. Acetyl-11-keto-ß-boswellic acid (AKBA), an active ingredient isolated from the plant Boswellia serrata, has been identified to induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we found that low concentrations of AKBA treatment triggered cell growth arrest at G0/G1 phase with features of premature cellular senescence phenotype in both HCC cell lines HepG2 and SMMC7721, as observed by enlarged and flattened morphology, significant increase in cells with senescence-associated ß-galactosidase staining, and decrease in cell proliferation and DNA synthesis. Furthermore, cellular senescence induced by AKBA occurred via activation of DNA damage response and impairment of DNA repair, as evidenced by strong induction of γH2AX and p53, and downregulated expressions of multiple DNA repair associated genes. Induction of p53 by AKBA caused a significant increase in p21CIP1 , which had a critical involvement in the induction of cellular senescence. Additionally, in vivo study demonstrated that induction of senescence contributed to the anticancer efficacy of AKBA. Therefore, our findings suggested that induction of premature senescence by AKBA through DNA damage response accompanied by impairment of DNA repair genes defines a novel mechanism contributing to its growth suppression in HCC cells.

Talin1 knockdown prohibits the proliferation and migration of colorectal cancer cells via the EMT signaling pathway.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second highest cause of cancer-associated death worldwide. Talin1 activates integrins, which mediate cell adhesion, proliferation, tumorigenesis and metastasis. The aim of the present study was to determine talin1 expression levels in colorectal cancer (CRC) and investigate the role of talin1 in CRC proliferation and invasion in vitro and in vivo. Talin1 protein expression levels were detected in human CRC and adjacent normal tissues by immunohistochemistry. Talin1 short hairpin RNA and control vectors were designed and stably transfected into HCT116 CRC cells. Cell proliferation was determined by MTT assay. Cell migratory and invasive capabilities were detected by wound-healing and Matrigel invasion assays. The expression of proteins in the epithelial-to-mesenchymal transition signaling pathway was determined by western blotting and reverse transcription-quantitative PCR. The effect of talin1 on tumor growth was explored in vivo using BALB/c nude mice. Immunohistochemical analysis of CRC and adjacent normal tissue revealed that talin1 expression was upregulated in CRC. Talin1 knockdown significantly reduced the proliferation, migration and invasive ability of HCT116 cells compared with the control. Protein levels of phosphorylated STAT3 and vimentin were significantly lower in talin1-knockdown HCT116 cell lines compared with the control, whereas protein levels of E-cadherin were increased. Interleukin-6 mRNA levels were significantly increased in patients' blood samples compared with blood samples from healthy controls, as well as in CRC compared with adjacent normal tissue. In vivo experiments demonstrated that talin1 knockdown reduced CRC tumor growth and weight in nude mice. In conclusion, Talin1 knockdown may prevent the proliferation and migration of CRC cells by downregulating various factors involved in the epithelial-to-mesenchymal transition process, such as phosphorylated STAT3 and vimentin; therefore, talin1 may provide a novel therapeutic target for CRC.

Induction of ROS and DNA damage-dependent senescence by icaritin contributes to its antitumor activity in hepatocellular carcinoma cells.

Context: Icaritin (ICT), a prenylflavonoid derivative extracted from the Epimedium (Berberidaceae) genus, has been identified to exhibit antitumor effect in hepatocellular carcinoma (HCC) cells by inducing apoptosis. However, its effect on cellular senescence has not been elucidated. Objective: To investigate the mechanism for low concentrations of ICT exerting antitumor activity through induction of cellular senescence. Materials and methods: Human HepG2 and Huh7 cells were treated with low concentrations of ICT (1 and 2 µM) once per day for a week. Cellular senescence was evaluated through cell viability and senescence-associated-ß-galactosidase activity. Cell cycle distribution and ROS levels were measured with flow cytometry. Gene expression was detected using qRT-PCR and western blotting. Fluorescent punctuates formation of γH2AX was analyzed by immunofluorescence. Results: ICT (1 and 2 µM) promoted cellular senescence in HepG2 and Huh7 cells, as observed by enlarged and flattened morphology and increased senescence-associated-ß-galactosidase activity (∼7-8-fold and ∼11-12-fold of vehicle controls, respectively), accompanied by significant cell cycle arrest and decrease in DNA synthesis. Mechanistically, ICT-induced senescence occurred through accumulation of ROS (∼1.3-fold and ∼1.8-fold of vehicle controls in response to 1 and 2 µM ICT, respectively), which further resulted in DNA damage response, as evidenced by strong induction of γH2AX through immunofluorescence and western blotting assays. Pharmacological inhibition of ROS production with N-acetylcysteine attenuated ICT-induced γH2AX and senescence-associated-ß-galactosidase activity (∼0.28-0.30-fold decrease, p < 0.05). Discussion and conclusions: Induction of cellular senescence by ICT defines a novel anticancer mechanism of ICT and provides a rationale for generalizing the study design to a broader study population to further developing ICT as a novel therapeutic agent for treatment of HCC.

Experimental study in vivo ablation of swine pancreas using high-intensity focused ultrasound.

OBJECTIVE: The objective of this study is to evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) for ablation of swine pancreas and to detect the pathological variations in pancreas damage. MATERIALS AND METHODS: (a) Eight swine were involved and randomly divided into two groups (Group A and B). HIFU was applied on swine in both groups for in vivo ablation of pancreas. The animals were anesthetized, and the artificial acoustic window was built. Then, the irradiation of FEP-BY02 type HIFU on pancreas was applied. (b) Swine in Group A were euthanized immediately after treating with HIFU to examine variations in pancreas. The biochemical evidence of pancreatitis was evaluated by blood samples collected from swine in Group B before and after HIFU. Then, the pancreas of swine in Group B was euthanized on day 5 after treatment to examine the pancreas. All specimens were visually inspected for both ultrasonic focal damage region (UFDR) and pathological routine by a skilled pathologist. RESULTS: (a) The vital signs of all animals were stable during HIFU treatment and recovered well after treatment. (b) UFDR were observed in all HIFU irradiation region of the specimens, without significant size difference between the two groups. The coagulation nucleus pyknosis, cytochylema vacuolation, and nucleus membrane disruption were observed after HIFU in both groups. Membranous structure dissolution and inflammatory cell infiltration were also found after HIFU in swine of Group B. (c) There was no significant difference in the levels of blood amylase in swine of Group B before and after HIFU treatment. CONCLUSIONS: It was feasible and safe to use HIFU for ablation of the pancreas in swine.

Relationship between the expressions of PD-L1 and tumour-associated fibroblasts in gastric cancer.

Previous studies have focused on the changes of tumour cells in immune escape, and less is known about the effect of tumour microenvironment (TME) on immune escape. Tumour-associated fibroblasts (TAF) is an important part of the TME and has special physiological and biochemical characteristics, but the specific mechanism has not been clarified. In order to investigate the effect of TAF on the expression of PD-L1 in gastric cancer cells, gastric cancer cell lines MNK45, SGC7901 were non-contact co-culturing with TAF 1, 3 and 7 d via transwell. PD-L1 mRNA and protein expression were detected using qRT-PCR and FCM. Then, 95 cases of gastric cancer tissues were selected and evaluated PD-L1 and TAF expressions by immunohistochemical examination. The results showed that the mRNA and protein expression of PD-L1 in the experiment group were significantly higher than that in the control group. PD-L1 expression was associated with massive lymphocyte infiltration, diffuse/mixed histology and intratumoral TAFs in gastric cancers. In conclusion, TAFs promoted the growth in gastric cancer cell lines by increased the PD-L1 expression.

LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2.

LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.

Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation.

BACKGROUND: Researches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach. METHODS: Transwell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot. RESULTS: Androgen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling. CONCLUSIONS: This study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro. Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.

Hollow S-nitrosothiols nanoparticle with polymeric brushes for nitric oxide (NO)-releasing as tumor targeted chemotherapy.

A kind of tumor targeting nitric oxide donor nanoparticle with brushes is described in this paper. The poly(4-vinylphenylboronic acid) polymeric brush, which shows glucose and pH dual responsiveness, endows the ability of hollow S-nitrosothiols nanoparticle to accurate recognition and binding with the sialic acid over-expressed type tumor cells, such as HepG2 and MCF-7 cells. In vitro experiments, including cells capture and release experiments, confocal fluorescence microscope characterization, cytotoxicity assay with different cells, demonstrate the selective recognition and the controlled NO release to kill tumor cells for these S-nitrosothiols nanoparticles. Low concentration of the released NO from the S-nitrosothiols nanoparticles in the transmission would participate physiological activity and avoid serious side effects because the endogenous nature and the physiological necessity to regulate normal biological functions. To the best of our knowledge, this is the first report about polymer nanoparticles as NO donors with functional brushes to selectively identify tumor cells and release NO in a controlled manner.