Abstract

// Yu Zhu 1 and Ping Yang 1 1 Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin 300350, P.R. China Correspondence to: Yu Zhu, email: zhuyutj@126.com Ping Yang, email: tjhhhospitallab@126.com Keywords: glioma; isothiocyanate; lncRNAs; circRNAs; proliferation Received: November 08, 2017 Accepted: December 26, 2017 Published: January 02, 2018 ABSTRACT Gliomas proliferation and invasion plays the critical roles in the tumor progression. Isothiocyanate is the hydrolysis products of Brassica vegetables and suppress many types of tumor including gliomas. We design and synthesized an isothiocyanate derivative by computer-aided drug design base on alkylglycerone phosphate synthase (AGPS) to improve targeting and explore its effect on the proliferation, invasion, apoptosis, cell cycle, and the expression of circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) in U251 cell line. The isothiocyanate derivative suppressed proliferation and invasion by inducing apoptosis with improving the activity of caspase-3/8 and blocked the cell cycle at G2/M phase and regulating the expression of circRNAs and lncRNAs involved in the above biological behavior in human glioma U251 cells. Our results showed the effect of isothiocyanate derivative on the anti-tumor activity, which shows potential for application as a anti-glioma drug.

Highlights

  • Glioma is one of the most common malignant tumors seriously damaging human’s health

  • The isothiocyanate derivative suppressed proliferation and invasion by inducing apoptosis with improving the activity of caspase-3/8 and blocked the cell cycle at G2/M phase and regulating the expression of circRNAs and long non-coding RNAs (lncRNAs) involved in the above biological behavior in human glioma U251 cells

  • Many previous studies of isothiocyanate were conducted on the apoptosis and inhibit proliferation and metastasis of tumor cells [6]. We found that it could inhibit the expression of alkylglycerone phosphate synthase (AGPS) which was an oncogene and the proliferation and invasion of tumor cells can be inhibited and the drug sensibility of drug resistant cells can be improved by AGPS silencing in our previous study [7,8], we found that AGPS silencing could regulate the expression of circRNAs and lncRNAs of U251 cell line

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Summary

Introduction

Glioma is one of the most common malignant tumors seriously damaging human’s health. Major advances have been made in the study of relevant clinical treatments, the prognosis is still not ideal [1]. Tumor metastasis is one of the primary reasons for treatment failure. Nearly half of the patients were diagnosed with advanced glioma, and there was the metastasis [2]. It is of great significance to develop new drugs to inhibit proliferation and metastasis. It was considered that circular RNAs (circRNAs) [3] and long non-coding RNAs (lncRNAs) [4] were an important role in tumor process, changed expression of them could improve or suppress the potential of proliferation and invasion in glioma. It is considered that circRNAs and lncRNAs were important target of tumor, including glioma

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