Oncology Research 24(4) Abstracts

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Oncology Research, Vol. 24, pp. 215-223, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X14634208143021
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Induction of Multidrug Resistance of Acute Myeloid Leukemia Cells by Cocultured Stromal Cells via Upregulation of the PI3K/Akt Signaling Pathway

Ping Chen,* Qing Jin,* Qiang Fu,* Peidong You,* Xi Jiang,* Qin Yuan,* and Huifang Huang†

*Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fujian, P.R. China
†Central Laboratory, Fujian Medical University Union Hospital, Fujian, P.R. China

This study aimed to investigate the role of the PI3K/Akt signaling pathway in multidrug resistance of acute myeloid leukemia (AML) cells induced by cocultured stromal cells. Human AML cell lines HL-60 and U937 were adhesion cocultured with human bone marrow stromal cell line HS-5 cells. Such coculturing induced HL-60 and U937 cells resistant to chemotherapeutic drugs including daunorubicin (DNR), homoharringtonine (HHT), and cytosine arabinoside (Ara-C). The coculturing-induced resistance of AML cells to DNR, HHT, and Ara-C can be partially reversed by inhibition of the PI3K/Akt signaling pathway. Clinically, AML patients with a low level of PTEN and a high level of CCND1 had high relapse rates within 1 year, and newly diagnosed AML patients with extramedullary infiltration had a low level of PTEN. This study confirms the involvement of the PI3K/Akt signaling pathway in multidrug resistance in AML cells induced by stroma and suggests that the expression of PTEN and CCND1 may be a prognostic indicator for AML.

Key words: Acute myeloid leukemia (AML); HS-5 cells; Multidrug resistance; PI3K/Akt signaling pathway

Address correspondence to Professor Huifang Huang, Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian 350001, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 225-231, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14648701447931
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

IGF-I Induces Epithelial-to-Mesenchymal Transition via the IGF-IR–Src–MicroRNA-30a–E-Cadherin Pathway in Nasopharyngeal Carcinoma Cells

Ruoyu Wang,*† Heming Li,† Xuefen Guo,† Zhe Wang,† Shanshan Liang,† and Chengxue Dang*

*Department of Surgical Oncology, The First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, P.R. China
†Department of Oncology, Zhongshan Hospital of Dalian University, Dalian, P.R. China

Recurrence and distant metastasis are the most common cause of therapeutic failure in nasopharyngeal carcinoma (NPC) patients. Insulin-like growth factor I (IGF-I) can induce epithelial-to-mesenchymal transition (EMT) in many epithelial tumors; however, whether IGF-I can enhance NPC metastasis by EMT and the mechanisms remain unclear. Herein, we have identified that IGF-I could induce EMT and enhance migration ability in NPC cell lines. Furthermore, both Src inhibitor and microRNA-30a (miR-30a) inhibitor reversed IGF-I-induced EMT, suggesting the involvement of an IGF-IR–Src–miR-30a–E-cadherin pathway in IGF-I-induced EMT in NPC cell lines. Overall, the results of the present study may provide more useful information regarding the mechanisms of the IGF-IR signaling pathway in the regulation of NPC metastasis. Both Src kinase and miR-30a can be potential biomarkers for selecting high risk of metastasis in NPC patients.

Key words: Epithelial-to-mesenchymal transition (EMT); Insulin-like growth factor I (IGF-I); Insulin-like growth factor I receptor (IGF-IR); Src; MicroRNA-30a (miR-30a)

Address corresponding to Chengxue Dang, Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi'an 710049, P.R. China. Tel: 86-189-91232170; Fax: 86-411-62893203; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 233-238, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14648701447977
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Overexpression of miR-509 Increases Apoptosis and Inhibits Invasion via Suppression of Tumor Necrosis Factor-α in Triple-Negative Breast Cancer Hs578T Cells

Guoqiang Zhang,*1 Zengyan Liu,†1 Yong Han,* Xiaohong Wang,* and Zhenlin Yang*

*Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, P.R. China
†Department of Hematology, Affiliated Hospital of Binzhou Medical College, Binzhou, P.R. China

Triple-negative breast cancer (TNBC) is associated with high recurrence rates of metastasis and death. miR-509 has been reported to be a tumor suppressor in many cancers, but its effect in TNBC has not yet been identified. In this article, we explored the effects of miR-509 on the malignant phenotype of TNBC cells, including proliferation, apoptosis, migration, and invasion. We transiently transfected TNBC cells, Hs578T, with miR-509 mimic. Upon transfection, the expression of miR-509 was upregulated about 50-fold compared with cells transfected with scramble mimic. Overexpression of miR-509 inhibited cell proliferation, induced cell apoptosis, and suppressed cell invasion of Hs578T cells. Moreover, tumor necrosis factor-α (TNF-α) was involved in miR-509-mediated suppressive effects of TNBC cells, as being treated with TNF-a could partially abolish the suppressive effects of miR-509. Collectively, these data suggest that miR-509 could reverse the malignant phenotype of TNBC cells, probably by suppressing TNF-α.

Key words: miR-509; Tumor necrosis factor-α (TNF-α); Breast cancer (BC); Triple-negative breast cancer (TNBC)

1These authors provided equal contribution to this work.
Address correspondence to Dr. Zhenlin Yang, No. 661 Huanghesan Road, Bincheng District, Binzhou, Shandong 256603, P.R. China. Tel: +86-543-3256506; Fax: +86-543-3256506; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 239-245, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14648701448011
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma

Xin-sheng Cheng,*† Shi-bo Sun,* Feng Zhong,* Kun He,* and Jie Zhou*

*Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
†Department of Hepatobiliary Surgery, Shenzhen Nanshan Hospital Affiliated to Guangdong Medical University, Shenzhen, China

Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A-shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma.

Key words: Hepatocellular carcinoma (HCC); hSETD1A; Clinical samples; SMMC-7721; Cell function

Address correspondence to Jie Zhou, Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Guangzhou 510515, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 247-253, 2016
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DOI: http://dx.doi.org/10.3727/096504016X14652175055765
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Novel BRCA2-Interacting Protein, LIMD1, Is Essential for the

Centrosome Localization of BRCA2 in Esophageal Cancer Cell

Xiaobin Hou,*1 Tinghui Li,†1 Zhipeng Ren,* and Yang Liu*

*Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China
†Department of Dermatology, The 309th Hospital of Chinese PLA, Beijing, China

Mutation of breast cancer 2, early onset (BRCA2) has been identified as a vital risk factor for esophageal cancer (EC). To date, several proteins have been reported as BRCA2-interacting proteins and are associated with multiple biological processes. This study's aim was to identify a novel interactive protein of BRCA2 and to explore its functional roles in EC. A yeast two-hybrid screening was performed to identify a novel BRCA2-interacting protein. Glutathione-S-transferase (GST) pull-down analysis was performed to find out how the binding domain of BRCA2 interacts with LIM domains containing 1 (LIMD1). The interaction between LIMD1 and BRCA2 at the endogenous level was confirmed by using coimmunoprecipitation and immunobloting. Furthermore, two different sequences of short hairpin RNAs (shRNAs) against LIMD1 were transfected into the human EC cell line ECA109. Afterward, the effects of LIMD1 suppression on the centrosome localization of BRCA2 and cell division were analyzed using an immunofluorescence microscope. Results showed that LIMD1 was a novel BRCA2-interacting protein, and LIMD1 interacted with the conserved region of BRCA2 (amino acids 2,750–3,094) in vitro. Importantly, after interfering with the protein expression of LIMD1 in ECA109 cells, the centrosome localization of BRCA2 was significantly abolished and abnormal cell division was significantly increased. These results suggested that LIMD1 is a novel BRCA2-interacting protein and is involved in the centrosome localization of BRCA2 and suppression of LIMD1, causing abnormal cell division in EC cells.

Key words: BRCA2; LIMD1; Centrosome localization; Esophageal cancer (EC)

1These authors provided equal contribution to this work.
Address correspondence to Xiaobin Hou, Department of Thoracic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 255-261, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X14666990347356
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

TIPE2 Inhibits Hypoxia-Induced Wnt/β-Catenin Pathway Activation and EMT in Glioma Cells

Zhi-jun Liu,*1 Hong-lin Liu,*1 Hai-cun Zhou,† and Gui-cong Wang*

*Department of Neurosurgery, Huaihe Hospital of Henan University, Kaifeng, China
†The People’s Hospital of Yongcheng City, Henan Province, Yongcheng, China

Hypoxia-induced epithelial-to-mesenchymal transition (EMT) could facilitate tumor progression. TIPE2, the tumor necrosis factor-α (TNF-α)-induced protein 8-like 2 (also known as TNFAIP8L2), is a member of the TNF-α-induced protein 8 (TNFAIP8, TIPE) family and has been involved in the development and progression of several tumors. However, the effects of TIPE2 on the EMT process in glioma cells and the underlying mechanisms of these effects have not been previously reported. In our study, we assessed the roles of TIPE2 in the EMT process in glioma cells in response to hypoxia. Our results indicated that TIPE2 expression was significantly decreased in human glioma cell lines. TIPE2 overexpression significantly inhibited hypoxia-induced migration and invasion, as well as suppressed the EMT process in glioma cells. Furthermore, TIPE2 overexpression prevented hypoxia-induced expression of β-catenin, cyclin D1, and c-myc in human glioma cells. In summary, these data suggest that TIPE2 overexpression inhibited hypoxia-induced Wnt/β-catenin pathway activation and EMT in glioma cells.

Key words: TIPE2; Hypoxia; Glioma; Epithelial-to-mesenchymal transition (EMT)

1These authors provided equal contribution to this work.
Address correspondence to Hong-lin Liu, Department of Neurosurgery, Huaihe Hospital of Henan University, No. 8 of Bao Hubei, Kaifeng 475000, China. Tel: +86-0371-23906516; Fax: +86-0371-23906036; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 253-269, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X14666990347392
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Suppression of Ubiquitin-Specific Peptidase 17 (USP17) Inhibits Tumorigenesis and Invasion in Non-Small Cell Lung Cancer Cells

Shengchao Zhang, Jun Yuan, and Ruheng Zheng

Department of Chest Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai, China

Recently, deubiquitinating enzymes (DUBs) are emerging as new regulators in cancer progression. However, understanding of the involvement of DUBs in non-small cell lung cancer (NSCLC) is just beginning. In this study, we investigated the expression and biological function of ubiquitin-specific peptidase 17 (USP17) in NSCLC progression in vitro and in vivo. We found that the expression of USP17 was higher than in a normal control. We further efficiently depleted USP17 expression in two different NSCLC cells, A549 and H1299. The anchorage-independent growth ability of these cells, estimated by soft agar colony formation assay, was significantly reduced after USP17 knockdown. Moreover, Matrigel–Transwell analysis showed that suppression of USP17 decreased cell migration and invasion capacity. Molecular mechanism studies found that USP17 silencing downregulated the expression of matrix metalloproteases (MMP3 and MMP9) in NSCLC cells. Furthermore, animal model results showed that USP17 suppression inhibited NSCLC tumorigenesis and growth. Altogether, this study illustrates the important functions of USP17 in NSCLC and suggests that USP17 might be an attractive target for NSCLC therapy.

Key words: Ubiquitin-specific peptidase 17 (USP17); Non-small cell lung cancer (NSCLC); Tumorigenesis; Invasion; Matrix metalloproteases (MMPs)

Address correspondence to Shengchao Zhang, M.D., Department of Chest Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, No. 1158, East Gongyuan Road, Qingpu District, Shanghai 201700, China. Tel: +86-181-1601-6176; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 271-277, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X14666990347473
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Knockdown of CUL4B Suppresses the Proliferation and Invasion in Non-Small Cell Lung Cancer Cells

Xuguang Wang* and Zhe Chen†

*Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
†Department of Radiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China

Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, was found to be overexpressed in many types of tumors. However, the expression pattern and role of CUL4B in non-small cell lung cancer (NSCLC) remain largely unknown. Therefore, in the present study, we investigated the role of CUL4B in NSCLC, and the underlying mechanism was also explored. Our results showed that CUL4B was highly expressed in NSCLC cell lines. Silencing CUL4B obviously inhibited proliferation and migration/invasion of NSCLC cells, and it also suppressed the epithelial–mesenchymal transition (EMT) progress in NSCLC cells. Furthermore, knockdown of CUL4B significantly inhibited the expression of β-catenin, cyclin D1, and c-Mycin NSCLC cells. Taken together, these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC.

Key words: Cullin 4B (CUL4B); Non-small cell lung cancer (NSCLC); Invasion; Wnt/β-catenin pathway

Address correspondence to Zhe Chen, Department of Radiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China Tel: +86-0371-63934118; Fax: +86-0371-63934118; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 24, pp. 279-286, 2016
0965-0407/16 $90.00 +.00
DOI: http://dx.doi.org/10.3727/096504016X14666990347554
E-ISSN 1555-3906
Copyright ©2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Knockdown of PARP-1 Inhibits Proliferation and ERK Signals, Increasing Drug Sensitivity in Osteosarcoma U2OS Cells

Sheng Li, Zhengli Cui, and Xianfeng Meng

Department of Orthopedics, Shengli Oilfield Central Hospital, Dongying, Shandong, China

Poly(ADP-ribose) polymerase 1 (PARP-1) is reported to be involved in DNA repair and is now recognized as a key regulator in carcinogenesis. However, the potential role and the molecular mechanism underlying the effect of PARP-1 on osteosarcoma (OS) cells have not been elucidated. In this study, the results showed that knockdown of PARP-1 resulted in decreased cell proliferation, increased cell apoptosis, and G0/G1 phase arrest in U2OS cells. In addition, increased expression of active caspase 3 and Bax, but reduced Bcl-2, cyclin D1, and phosphorylated extracellular signal regulated kinase 1/2 (pERK1/2) were observed in PARP-1 knockdown in U2OS cells. Moreover, knockdown of PARP-1 correlated with elevated chemosensitivity of U2OS cells to cisplatin through inactivation of the ERK1/2 signaling pathway. In conclusion, our findings demonstrated that PARP-1 plays an important role in regulating OS growth, combining PARP-1 gene therapy with traditional chemotherapy, and may serve as a promising approach to OS therapy.

Key words: PARP-1; Osteosarcoma; Cisplatin; Chemoresistance; ERK1/2

Address correspondence to Xianfeng Meng, Department of Orthopedics, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying, Shandong 257034, China. Tel: +86-0546-8770971; Fax: +86-0546-8770971; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it