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    ARTICLE

    Exosomes Derived From Hypoxic Colorectal Cancer Cells Promote Angiogenesis Through Wnt4-Induced β-Catenin Signaling in Endothelial Cells

    Zhe Huang, Yong Feng
    Oncology Research, Vol.25, No.5, pp. 651-661, 2017, DOI:10.3727/096504016X14752792816791
    Abstract Cancer cell-derived exosomes have been actively released into the tumor microenvironment with pleiotropic roles in tumor growth and metastasis, including angiogenesis and immune modulation. However, the functions and underlying mechanisms of exosomes shed by colorectal cancer (CRC) cells under hypoxic conditions remain unknown. Here we found that exosomes derived from hypoxic CRC cells promoted the proliferation and migration of endothelial cells. Suppression of exosome secretion through RAB27a knockdown in CRC cells inhibited exosomal-induced proliferation and migration of endothelial cells. Furthermore, we discovered that these exosomes enriched with Wnt4 were dependent on HIF1α. Exosomal Wnt4 increased More >

  • Open AccessOpen Access

    ARTICLE

    PAQR3 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer Cells

    Fang Zhou*1, Shunchang Wang†1, Jianjun Wang*
    Oncology Research, Vol.25, No.5, pp. 663-671, 2017, DOI:10.3727/096504016X14761384026719
    Abstract Progestin and adipoQ receptor family member III (PAQR3), a member of the PAQR family, is frequently downregulated in different types of human cancer. However, its expression and functions in esophageal cancer are still unknown. This study aimed to explore the expression of PAQR3 in esophageal cancer cell lines and to investigate the role of PAQR3 in the development of esophageal cancer. Our data showed that PAQR3 is expressed in low amounts in human esophageal cancer cell lines. Overexpression of PAQR3 significantly suppressed the proliferation, migration, and invasion of esophageal cancer cells. In addition, overexpression of More >

  • Open AccessOpen Access

    ARTICLE

    Regorafenib Plus FOLFIRI With Irinotecan Dose Escalated According to Uridine Diphosphate Glucuronosyltransferase 1A1 Genotyping in Patients With Metastatic Colorectal Cancer

    Cheng-Jen Ma*†‡, Ching-Wen Huang*‡§, Yung-Sung Yeh*†¶, Hsiang-Lin Tsai*§#**, Huang-Ming Hu††‡‡, I-Chen Wu††‡‡, Tian-Lu Cheng§§¶¶, Jaw-Yuan Wang*†‡§**¶¶
    Oncology Research, Vol.25, No.5, pp. 673-679, 2017, DOI:10.3727/97818823455816X14786040691928
    Abstract We analyzed the results of previously treated patients with metastatic colorectal cancer (mCRC) who received regorafenib plus FOLFIRI with the irinotecan dose escalation on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping. Thirteen patients with previously treated mCRC were subjected to UGT1A1 genotyping between October 2013 and June 2015 and were administered regorafenib plus FOLFIRI with irinotecan dose escalation. Patients with UGT1A1*1/*1 and *1/*28 genotypes were administered 180 mg/m2 of irinotecan, whereas those with the UGT1A1*28/*28 genotype were administered 120 mg/m2 of irinotecan. For all patients, the irinotecan dose was increased by 30 mg/m2 every… More >

  • Open AccessOpen Access

    ARTICLE

    FOXR2 Promotes the Proliferation, Invasion, and Epithelial–Mesenchymal Transition in Human Colorectal Cancer Cells

    Sheng-Qiang Lu*1, Yan Qiu†1, Wei-Jie Dai, Xiao-Yu Zhang§
    Oncology Research, Vol.25, No.5, pp. 681-689, 2017, DOI:10.3727/096504016X14771034190471
    Abstract Forkhead box R2 (FOXR2), a member of the FOX gene family, has not been very well investigated for its role in cancer. A recent study has shown that FOXR2 is highly expressed in breast cancer samples and is associated with poor prognosis. In addition, FOXR2 was identified as an oncogene in medulloblastoma. Nevertheless, whether FOXR2 plays a role in colorectal cancer (CRC) remains unclear. In the present study, we conducted several in vitro and in vivo studies to investigate the expression and effect of FOXR2 in CRC. The study results demonstrated that FOXR2 was upregulated More >

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    ARTICLE

    TRIM11 Upregulation Contributes to Proliferation, Invasion, and EMT of Hepatocellular Carcinoma Cells

    Zewei Zhang*1, Chao Xu†1, Xiafang Zhang†1, Lulu Huang, Cheng Zheng, Haitao Chen, Yan Wang, Haixing Ju§, Qinghua Yao
    Oncology Research, Vol.25, No.5, pp. 691-699, 2017, DOI:10.3727/096504016X14774897404770
    Abstract The tripartite motif-containing protein 11 (TRIM11), a member of the TRIM protein family, has attracted much attention because of its involvement in the development of the central nervous system. It has gained renewed focus because of its newly found function in promoting tumors. However, little is known about its role in hepatocellular carcinoma (HCC). In the present study, we found TRIM11 to be overexpressed in HCC tissues and cell lines. Downregulation of TRIM11 inhibited HCC cell proliferation and invasion in vitro and in vivo as well as suppressed the epithelial–mesenchymal transition (EMT) process. In addition, More >

  • Open AccessOpen Access

    ARTICLE

    Forkhead Box A2 (FOXA2) Inhibits Invasion and Tumorigenesis in Glioma Cells

    Bingqian Ding*1, Huimin Liang†1, Ming Gao*, Zhenjiang Li*, Chenyang Xu*, Shaokang Fan*, Na Chang
    Oncology Research, Vol.25, No.5, pp. 701-708, 2017, DOI:10.3727/096504016X14772378087005
    Abstract The forkhead box A2 (FOXA2) is the key transcriptional factor that plays an important role in tumorigenesis. However, until now the expression pattern and role of FOXA2 in glioma have yet to be elucidated. Therefore, the aim of this study was to evaluate the expression of FOXA2 in glioma and investigate its role in glioma cells. Our data showed that FOXA2 was significantly downregulated in human glioma cell lines. Forced expression of FOXA2 suppressed the ability of glioma cells to proliferate, migrate, and invade and influenced the expression level of EMT-associated proteins. In addition, forced More >

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    ARTICLE

    Overexpression of PER3 Inhibits Self-Renewal Capability and Chemoresistance of Colorectal Cancer Stem-Like Cells via Inhibition of Notch and β-Catenin Signaling

    Feng Zhang*, Hong Sun, Sai Zhang, Xin Yang, Guogang Zhang*, Tao Su
    Oncology Research, Vol.25, No.5, pp. 709-719, 2017, DOI:10.3727/096504016X14772331883976
    Abstract PER3, a circadian clock gene, plays an important role in colorectal cancer, but its action and underlying mechanism in colorectal cancer stem-like cells (CSCs) remain unclear. In this study, the colorectal CSCs were enriched in colorectal HCT-116 sphere-forming cells, expressing lower levels of stem cell markers CD133, CD44, LGR5, and SOX2 compared with HCT-116 cells. A drug-resistant strain from HCT-116 was established. Western blot and qRT-PCR analysis showed that PER3 was downregulated in colorectal CSCs and drug-resistant HCT-116. Overexpression of PER3 could strengthen 5-FU-induced inhibitory effects on colorectal CSCs, but knockdown of PER3 decreased its… More >

  • Open AccessOpen Access

    ARTICLE

    Knockdown of Cyclin-Dependent Kinase Inhibitor 3 Inhibits Proliferation and Invasion in Human Gastric Cancer Cells

    Yan Li*, Shan Ji, Li-Ye Fu*, Tao Jiang*, Di Wu*, Fan-Dong Meng*
    Oncology Research, Vol.25, No.5, pp. 721-731, 2017, DOI:10.3727/096504016X14772375848616
    Abstract Cyclin-dependent kinase inhibitor 3 (CDKN3) has been reported to promote tumorigenesis. Since it is unclear whether CDKN3 participates in the development of human gastric cancer, this study assessed the association between CDKN3 expression and cell biological function and demonstrated the clinical significance and prognosis of CDKN3 in human gastric cancer. In this study, we found that CDKN3 showed a high expression in 35 paired human gastric cancer tissues and was correlated with poor patient survival, AJCC clinical staging, and recurrence. Silencing of CDKN3 in human gastric cancer cells can significantly reduce proliferation, migration, invasion, and More >

  • Open AccessOpen Access

    ARTICLE

    Long Noncoding RNA LINC00261 Suppresses Cell Proliferation and Invasion and Promotes Cell Apoptosis in Human Choriocarcinoma

    Yinan Wang*, Kai Xue, Yonghong Guan*, Yuemei Jin*, Shanshan Liu*, Yichao Wang*, Shuyan Liu*, Ling Wang*, Liying Han*
    Oncology Research, Vol.25, No.5, pp. 733-742, 2017, DOI:10.3727/096504016X14772362173376
    Abstract Choriocarcinoma is one of the gestational trophoblastic neoplasias (GTNs) that originate in the chorionic villi and the extravillous trophoblast. Long noncoding RNAs (lncRNAs) are a type of non-protein-coding RNAs that have recently been implicated in human tumorigenesis. The present study investigated the role of the lncRNA LINC00261 in cell proliferation, metastasis, and apoptosis in choriocarcinoma cell lines. The transcription level of LINC00261 was significantly lower in choriocarcinoma tissues and in choriocarcinoma cell lines. Overexpression of LINC00261 caused a decrease in cell proliferation and arrested the cell cycle at the G0/G1 phase. Furthermore, overexpression of LINC00261 inhibited More >

  • Open AccessOpen Access

    ARTICLE

    Downregulation of Ubiquitin-Specific Protease 22 Inhibits Proliferation, Invasion, and Epithelial–Mesenchymal Transition in Osteosarcoma Cells

    Dengfeng Zhang1, Feng Jiang1, Xiao Wang, Guojun Li
    Oncology Research, Vol.25, No.5, pp. 743-751, 2017, DOI:10.3727/096504016X14772395226335
    Abstract Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, belongs to an extended family of proteins that have ubiquitin hydrolase activity. Recently, USP22 has attracted widespread attention because of its implication in carcinogenesis. However, there have been no studies, to our knowledge, investigating the expression of USP22 in osteosarcoma (OS) and its association with OS progression. In this study, we explored the role of USP22 in OS. We demonstrated that USP22 was highly expressed in OS tissue and cell lines. Downregulation of USP22 inhibited OS cell proliferation, invasion, and epithelial–mesenchymal transition (EMT) in vitro. In addition, More >

  • Open AccessOpen Access

    ARTICLE

    Downregulation of MicroRNA-449 Promotes Migration and Invasion of Breast Cancer Cells by Targeting Tumor Protein D52 (TPD52)

    Zhiling Zhang, Jiawei Wang, Runfang Gao, Xuan Yang, Yafen Zhang, Jie Li, Jing Zhang, Xingjuan Zhao, Chunfang Xi, Xiaoting Lu
    Oncology Research, Vol.25, No.5, pp. 753-761, 2017, DOI:10.3727/096504016X14772342320617
    Abstract Our study aimed to investigate whether microRNA-449 (miR-449) plays a key role in regulating the migration and invasion of breast cancer cells via targeting tumor protein D52 (TPD52). The results of the qRT-PCR and Western blotting showed that, in comparison with normal breast tissues and cells, miR-449 was significantly downregulated in breast cancer tissues and cells, while TPD52 was markedly upregulated. After transfection with an miR-449 inhibitor, suppression of miR-449 significantly promoted cell migration and invasion. Also, when miR-449 was overexpressed by transfection with miR-449 mimics, E-cadherin expression significantly increased, and the expression of N-cadherin More >

  • Open AccessOpen Access

    ARTICLE

    Knockdown of SALL4 Inhibits Proliferation, Migration, and Invasion in Osteosarcoma Cells

    Dengfeng Zhang1, Feng Jiang1, Xiao Wang, Guojun Li
    Oncology Research, Vol.25, No.5, pp. 763-771, 2017, DOI:10.3727/096504016X14772402056137
    Abstract Sal-like protein 4 (SALL4) is a zinc finger transcription factor that has been reported to be aberrantly expressed in several human malignancies and identified as an oncogene. However, the potential role of SALL4 in osteosarcoma remains to be elucidated. In this study, we explored the biological functions of SALL4 in osteosarcoma. We found that SALL4 was overexpressed in osteosarcoma tissues and cell lines. Knockdown of SALL4 inhibited osteosarcoma cell proliferation, migration, and invasion in vitro. In addition, SALL4 knockdown suppressed osteosarcoma growth and metastasis in vivo. We also showed that SALL4 knockdown decreased the protein More >

  • Open AccessOpen Access

    ARTICLE

    Tumor Protein D52 (TPD52) Inhibits Growth and Metastasis in Renal Cell Carcinoma Cells Through the PI3K/Akt Signaling Pathway

    Zhenhua Zhao1, Hui Liu1, Junqing Hou, Tieqiang Li, Xinyi Du, Xiaolei Zhao, Wenchao Xu, Weibo Xu, Junkai Chang
    Oncology Research, Vol.25, No.5, pp. 773-779, 2017, DOI:10.3727/096504016X14774889687280
    Abstract Tumor protein D52 (TPD52) is a member of the TPD52-like protein family and plays different roles in various types of malignancies. However, its role in renal cell carcinoma (RCC) is still unclear. In this study, we investigated the role of TPD52 in RCC. The mechanism of TPD52 in RCC was also investigated. Our data demonstrated that the expression levels of TPD52 in both mRNA and protein were significantly decreased in RCC cells. Overexpression of TPD52 inhibited proliferation, migration, and invasion with decreased epithelial–mesenchymal transition (EMT) phenotype in RCC cells, as well as attenuated tumor growth More >

  • Open AccessOpen Access

    ARTICLE

    Protease Serine S1 Family Member 8 (PRSS8) Inhibits Tumor Growth In Vitro and In Vivo in Human Non-Small Cell Lung Cancer

    Chaonan Ma*1, Wei Ma*1, Nannan Zhou*, Na Chen*, Li An, Yijie Zhang*
    Oncology Research, Vol.25, No.5, pp. 781-787, 2017, DOI:10.3727/096504016X14772417575982
    Abstract Protease serine S1 family member 8 (PRSS8), a membrane-anchored serine protease, has been reported to be involved in the development of several human cancers. However, the role of PRSS8 in non-small cell lung cancer (NSCLC) pathogenesis remains unclear. The objective of this study was to investigate PRSS8 expression, biological function, and its related molecular mechanism in NSCLC. Our results showed that PRSS8 was expressed in a low amount in NSCLC cell lines. Ectopic expression of PRSS8 inhibited tumor growth in vitro and in vivo. Furthermore, ectopic expression of PRSS8 inhibited the migration and invasion of More >

  • Open AccessOpen Access

    ARTICLE

    Long Noncoding RNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation and Invasion in Gastric Cancer via Negatively Modulating miRNA-145-5p

    Kewei Ren*†‡, Zhen Li*†‡, Yahua Li*†‡, Wenzhe Zhang*†‡, Xinwei Han*†‡
    Oncology Research, Vol.25, No.5, pp. 789-798, 2017, DOI:10.3727/096504016X14783677992682
    Abstract Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is involved in the development and carcinogenesis of various tumors, suggesting the diagnostic potential of TUG1 in these cancers. However, the exact role of TUG1 and its underlying mechanism in gastric cancer (GC) remain unknown. In this study, the expression of TUG1 and miR-145-5p in GC cell lines and nonmalignant gastric epithelial cell lines was detected by qRT-PCR. BGC-823 and SGC-7901 cells were transfected with si-TUG1, pcDNA 3.1-TUG1, miR-145-5p mimics, or matched controls. The biological function of TUG1 and miR-145-5p in GC cell proliferation and invasion in… More >

  • Open AccessOpen Access

    ARTICLE

    Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer Growth Through Induction of ER Stress, Inhibition of Wnt Signaling, and Activation of Apoptosis

    Xiaohe Guo*, Lanfang Zhang*, Yingying Fan*, Dezhong Zhang, Lei Qin*, Shuping Dong*, Guangyan Li*
    Oncology Research, Vol.25, No.5, pp. 799-808, 2017, DOI:10.3727/096504016X14783691306605
    Abstract Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Oxysterol-binding proteinrelated protein 8 (ORP8) functions as a sterol sensor that regulates a number of cellular functions. We showed that ORP8 expression was significantly lower in GC tissues and cells. Overexpression of ORP8 significantly inhibited GC cell proliferation in several GC cells. The formation of colonies in AGS cells was inhibited by the overexpression of ORP8. Moreover, overexpression of ORP8 significantly decreased implanted tumor growth in nude mice. Overexpression of ORP8 resulted in a significant increase in CHOP and GRP78 expression and the… More >

  • Open AccessOpen Access

    ARTICLE

    Kallistatin Suppresses Cell Proliferation and Invasion and Promotes Apoptosis in Cervical Cancer Through Blocking NF-κB Signaling

    Tao Wang, Fan Shi, JiQuan Wang, Zi Liu, Jin Su
    Oncology Research, Vol.25, No.5, pp. 809-817, 2017, DOI:10.3727/096504016X14799180778233
    Abstract Kallistatin has been recognized as an endogenous angiogenesis inhibitor and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis, and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activities and markedly reduced the expression of matrix-degrading metalloproteinases, progelatinase (MMP-2), MMP-9, and urokinase-type PA (uPA). Kallistatin reversed the epithelial–mesenchymal transition (EMT) and caused the upregulation of epithelial markers such as E-cadherin and inhibited… More >

  • Open AccessOpen Access

    ARTICLE

    Silencing of Btbd7 Inhibited Epithelial–Mesenchymal Transition and Chemoresistance in CD133+ Lung Carcinoma A549 Cells

    Li-Zhou Fang*, Jian-Qing Zhang*, Ling Liu*, Wei-Ping Fu*, Jing-Kui Shu*, Jia-Gang Feng*, Xiao Liang
    Oncology Research, Vol.25, No.5, pp. 819-829, 2017, DOI:10.3727/096504016X14772349843854
    Abstract Cancer stem cells (CSCs) are responsible for tumorigenesis and recurrence, so targeting CSCs is an effective method to potentially cure cancer. BTB/POZ domain-containing protein 7 (Btbd7) has been found in various cancers, including lung cancer and liver cancer, but the role of Btbd7 in non-small cell lung cancer (NSCLC), CSC self-renewal, and chemoresistance is still unknown. Therefore, in this study we found that the ratio of tumor sphere formation and stem cell transcription factors in CD133+ cells was dramatically enhanced compared to parental cells, which indicated successful sorting of CD133+ cells from A549. Meanwhile, Btbd7 and More >

  • Open AccessOpen Access

    ARTICLE

    GGNBP2 Suppresses the Proliferation, Invasion, and Migration of Human Glioma Cells

    Ao Zhan*, Bo Lei*, Honggang Wu*, YueTao Wen, Liandong Zheng*, Shan Wang*, Xiaoqiang Wan*, Zhenghong Wei*
    Oncology Research, Vol.25, No.5, pp. 831-842, 2017, DOI:10.3727/096504016X14816726393937
    Abstract Gliomas are the most common and aggressive type of primary adult brain tumors. Although GGNBP2 has previously been considered to be a tumor suppressor gene, little is known about the association between GGNBP2 and glioma. In this study, we clearly demonstrated that GGNBP2 was downexpressed in glioma tissues, and its downexpression is related to the pathological grade and overall survival of patients with gliomas. Overexpression of GGNBP2 suppressed the proliferation, migration, and invasion of glioma cells. Mechanistically, we demonstrated that the PI3K/Akt and Wnt/β-catenin signaling pathways were suppressed by GGNBP2 overexpression. In contrast, knockdown of More >

  • Open AccessOpen Access

    ARTICLE

    Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial–Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells

    Wenzhang Zhang*1, Xin Wu†1, Liang Hu*, Yuefan Ma*, Zihan Xiu*, Bingyu Huang*, Yun Feng*, Xudong Tang*†‡
    Oncology Research, Vol.25, No.5, pp. 843-852, 2017, DOI:10.3727/096504016X14813880882288
    Abstract The human papillomavirus (HPV) infection may be associated with the development and progression of nonsmall cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial–mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed… More >

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