Oncology Research 23(3) Abstracts

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Oncology Research, Vol. 23, pp. 89-98, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14496932933539
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Inhibition of Migration and Invasion by Tet-1 Overexpression in Human Lung Carcinoma H460 Cells

Si Jun Park,*1 Bo Ram Lee,*1 Hyeng-Soo Kim,* Young Rae Ji,* Yong Hun Sung,* Kwang ShikChoi,* Hum Dai Park,† Sung-Hyun Kim,* Myoung Ok Kim,‡ and Zae Young Ryoo*

*School of Life Science, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Buk-ku, Daegu, Republic of Korea
†Department of Biotechnology, School of Engineering, Daegu University, GyeongsangGyeongbuk, Republic of Korea
‡School of Animal BT Sciences, Sangju Campus, Kyungpook National University, SangjuGyeongsangbuk-do, Republic of Korea

In the present study, we found that lung cancer cell line (H460 cells) expressing Tet1 showed higher levels of adhesion, and Tet1 inhibited H460 cell proliferation. In addition, these cells showed a significantly reduced ability of collagen degradation and Smad2/3 phosphorylation compared to controls. Furthermore, vimentin was found to be highly expressed in larger metastatic cancer area. Tet1 overexpression was reduced in the epithelial marker E-cadherin. Moreover, Tet1 repressed cancer cell metastasis in nude mice. Collectively, these findings suggest that Tet1 expression plays a critical role in metastasis of lung cancer cells by suppression of invasion and epithelial–mesenchymal transition (EMT).

Key words: Tet1; Demethylation; Lung cancer; Epithelial–mesenchymal transition (EMT); Metastasis

1These authors provided equal contribution to this work.
Address correspondence to Zae Young Ryoo, School of Life Science, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Buk-ku, Daegu 702-701, Republic of Korea. Tel: +82 53 950 7361; Fax: +82 53 943 6925; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  orMyoung Ok Kim, School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, SangjuGyeongsangbuk-do 742-211, Republic of Korea. Tel: +82 53 950 7361; Fax: +82 53 943 6925; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 99-107, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14496932933575
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Long Noncoding RNA H19-Derived miR-675 Enhances Proliferation and Invasion via RUNX1 in Gastric Cancer Cells

Gao Liu,* Tian Xiang,† Quan-Feng Wu,‡ and Wei-Xing Wang*

*Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
†Department of Clinical Laboratory Center, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China
‡Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China

The lncRNA H19 and its mature product miR-675 have recently been shown to be upregulated and promote the progression of gastric cancer. However, the detailed function and underlying molecular mechanism of H19/miR-675 in the carcinogenesis of gastric cancer remains unclear. In this study, we found that H19 depended on miR-675 to enhance the proliferation and invasion of gastric cancer AGS cells, and the expression of miR-675 was positively correlated with H19 in patients with gastric cancer. Subsequently, the tumor-suppressor runt domain transcription factor 1 (RUNX1) was confirmed to be a downstream molecule of H19/miR-675 axis, since overexpression of H19 or miR-675 significantly decreased RUNX1 expression in AGS cells, and knockdown of H19 or miR-675 enhanced RUNX1 expression. More importantly, a series of assays further demonstrated that introduction of RUNX1 abrogated H19/miR-675-induced Akt/mTOR pathway activation and the following cellular proliferation and invasion of AGS cells. To our knowledge, this is the time to demonstrate that RUNX1 serves as a link between H19/miR-675 axis and Akt/mTOR signaling and is a pivotal mediator in gastric cancer progression induced by H19/miR-675. Thus, our study provides important clues for understanding the key roles of lncRNA-miRNA functional network and identifying new therapeutic targets for gastric cancer.

Key words: H19; miR-675; Runt domain transcription factor 1 (RUNX1); Akt/mTOR pathway; Gastric cancer

Address correspondence to Professor Wei-Xing Wang, Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 109-118, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14496932933610
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

ERK Signaling Pathway Is Involved in HPV-16 E6 but not E7 Oncoprotein-Induced HIF-1α Protein Accumulation in NSCLC Cells

Fei Liu,*1 Bihua Lin,*1 Xin Liu,* Wenzhang Zhang,* Erying Zhang,* Liang Hu,* Yuefan Ma,* Xiangyong Li,* and Xudong Tang*†

*Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong, China
†Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Zhanjiang, Guangdong, China

Extracellular signal-regulated kinase (ERK)1/2 signaling pathway plays a critical role in regulating tumor angiogenesis. Our previous studies have demonstrated that HPV-16 oncoproteins enhanced hypoxia-inducible factor-1α (HIF-1α) protein accumulation and vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells, thus contributing to angiogenesis. In this study, we further investigated the role of ERK1/2 signaling pathway in HPV-16oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in NSCLC cells. Our results showed that HPV-16 E6 and HPV-16 E7 oncoproteins promoted the activation of ERK1/2 signaling pathway in A549 and NCI-H460 cells. Moreover, PD98059, a specific inhibitor of ERK1/2, blocked in vitro angiogenesis stimulated by HPV-16 E6 but not E7 oncoprotein. Additionally, HIF-1α protein accumulation and VEGF and IL-8 expression in NSCLC cells induced by HPV-16 E6 but not E7oncoprotein were significantly inhibited by PD98059. Taken together, our results suggest that ERK1/2 signaling pathway is involved in HPV-16 E6 but not E7 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression in NSCLC cells, leading to the enhanced angiogenesis in vitro.

Key words: Extracellular signal-regulated kinases (ERK) 1/2; Human papillomavirus; Non-small cell lung cancer; Angiogenesis; Hypoxia-inducible factor-1α; Vascular endothelial growth factor (VEGF); Interleukin-8

1These authors provided equal contribution to this work.
Address correspondence to Professor Xudong Tang, Institute of Biochemistry and Molecular Biology, Guangdong Medical University, 2 Wenming DongluXiashan, Zhanjiang, Guangdong 524023, China. Tel: +86 13226269146; Fax: +86 759 2284104 E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 119-128, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14496932933656
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

HSP27 Knockdown Increases Cytoplasmic p21 and Cisplatin Sensitivity in Ovarian Carcinoma Cells

Hao Lu,1 Chaoyang Sun,1 Ting Zhou, Bo Zhou, Ensong GuoWanying Shan, Meng Xia, Kezhen Li, Danhui Weng, Li MengXiaoyan Xu, Junbo Hu, Ding Ma, and Gang Chen

Cancer Biology Medical Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Drug resistance is the leading cause of chemotherapy failure in the treatment of ovarian cancer. So far, little is known about the mechanism of chemoresistance in ovarian cancer. In this study, we explored the mechanism that HSP27 was involved in cisplatin resistance of ovarian cancer both in vitro and clinically. HSP27 protein was found to be upregulated and expressed in cisplatin-resistant ovarian cancer cell line C13*, and HSP27 siRNA transfection reversed the chemoresistance of C13*. We found that HSP27 exerted its chemoresistant role by inhibiting p21 transferring from the nucleus to the plasma through the activation of phosphorylated-Akt pathway. These findings have implications for clinical trials aimed at a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.

Key words: Cisplatin; Ovarian cancer; HSP27; p21

1These authors provided equal contribution to this work.
Address correspondence to Dr. Chen Gang, Cancer Biology Medical Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Fax: +86-27-83663351; Tel: +86-27-83662681; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 129-136, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14500513118029
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells

Qun Zhao, Bi-Bo Tan, Yong Li, Li-Qiao Fan, Pei-Gang Yang, and Yuan Tian

Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China

In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-specific siRNA was synthetized and transfected into drug-resistant GC cell line OCUM-2MD3/L-OHP. Then MTT assay was applied to test the inhibition rate of GC cells by 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). After that, flow cytometry (FCM) was applied to measure apoptosis rate. qPCR and Western blot assay were employed to detect HIF-1α and apoptosis-related genes. Results showed that HIF-1α in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1α-siRNA transfection, inhibition rates of 5-FU and L-OHP to tumor cells increased significantly. FCM results showed that apoptosis rate of OCUM-2MD3/L-OHP cells increased significantly. After HIF-1α-siRNA transfection, survivin and Bcl-2 decreased, whereas Bax, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1α getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1α may be a potential target to reverse drug resistance of GC.

Key words: Gastric carcinoma (GC); Hypoxia-inducible factor-1α; Drug resistance; Drug sensitivity test in vitro; Apoptosis-related genes

Address correspondence to Yong Li, Department of General Surgery, the Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang 050011, China. Tel: +86-311-86095678; Fax: +86-311-86077634; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 23, pp. 137-146, 2016
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DOI: http://dx.doi.org/10.3727/096504015X14500972666761
E-ISSN 1555-3906
Copyright ©
2016 Cognizant, LLC. 
Printed in the USA. All rights reserved

Flow Cytometric Evaluation of Double/Triple Hit Lymphoma

Christine G. Roth,* Amanda Gillespie-Twardy,† Stanley Marks,† Mounzer Agha,† Anastasios Raptis,† Jing-Zhou Hou,† Rafic Farah,† Yan Lin,§ Ying Qian,§ Liron Pantanowitz,‡ and Michael Boyiadzis

*Department of Pathology, Division of Hematopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
†Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
‡Department of Pathology, Division of Cytopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
§Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

“Double” or “triple” hit lymphomas (D/THL) with recurrent translocations involving MYC/8q24 and BCL2/18q21 and/or BCL6/3q27 are characterized by a poor prognosis, but their identification is hampered by the clinicopathologic overlap with other disease categories. Cases with circulating blastic-appearing cells may initially cause concern for lymphoblastic leukemia a diagnostic dilemma, which has not been well studied. There is only limited literature regarding the flow cytometric (FC) D/THL phenotype and its clinical correlates. The FC features of 20 D/THL (11 BCL2+/MYC+, 5 BCL6+/MYC+, 4 CL2+/BCL6+/MYC+) were evaluated, compared to 20 B-lymphoblastic leukemias (B-LBL), and correlated with overall survival. Most (89%, 17/19) D/THL were CD10+, 47% (9/19) lacked surface light chain, and a significant subset underexpressed CD45 (47%, 9/19), CD20 (42% 8/19), and/or CD19 (39%, 7/18), which did not vary by genetic subgroup. Compared to B-LBL, D/THL less frequently underexpressedCD45 (p = 0.0001) and CD20 (p = 0.0004). Lower levels of BCL2 expression were noted in the BCL6+/MYC+
and BCL2+/BCL6+/MYC+ subgroups versus BCL2+/MYC+ cases (p = 0.0014). Of the flow cytometric parameters assessed, dim CD45 expression correlated with inferior survival (p = 0.01). Although there is some overlap with B-LBL, D/THL demonstrates a characteristic immunophenotype which may have prognostic significance and warrants further investigation.

Key words: Double hit lymphoma; MYC; BCL2; BCL6

Address correspondence to Christine G. Roth, M.D., UPMC-PUH G300, 200 Lothrop Street, Pittsburgh, PA 15213, USA. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it