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Article

Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness

by
Yu-Kai Su
1,2,3,4,†,
Jia Wei Lin
1,2,3,4,†,
Jing-Wen Shih
5,6,
Hao-Yu Chuang
7,
Iat-Hang Fong
2,3,4,
Chi-Tai Yeh
1,8,9 and
Chien-Min Lin
1,2,3,4,*
1
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan
2
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan
3
Division of Neurosurgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan
4
Taipei Neuroscience Institute, Taipei Medical University, Taipei City 11031, Taiwan
5
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
6
Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
7
Department of Neurosurgery, An Nan Hospital, China Medical University, Tainan 70965, Taiwan
8
Department of Medical Research & Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan
9
Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2020, 9(8), 1859; https://doi.org/10.3390/cells9081859
Submission received: 15 May 2020 / Revised: 15 July 2020 / Accepted: 4 August 2020 / Published: 8 August 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Glioblastoma)
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Abstract

Background: Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results: Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.
Keywords: non-coding RNA; noncoding RNA BC200/miR-218-5p signaling circuit; glioblastoma stem cells; temozolomide resistance non-coding RNA; noncoding RNA BC200/miR-218-5p signaling circuit; glioblastoma stem cells; temozolomide resistance
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MDPI and ACS Style

Su, Y.-K.; Lin, J.W.; Shih, J.-W.; Chuang, H.-Y.; Fong, I.-H.; Yeh, C.-T.; Lin, C.-M. Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness. Cells 2020, 9, 1859. https://doi.org/10.3390/cells9081859

AMA Style

Su Y-K, Lin JW, Shih J-W, Chuang H-Y, Fong I-H, Yeh C-T, Lin C-M. Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness. Cells. 2020; 9(8):1859. https://doi.org/10.3390/cells9081859

Chicago/Turabian Style

Su, Yu-Kai, Jia Wei Lin, Jing-Wen Shih, Hao-Yu Chuang, Iat-Hang Fong, Chi-Tai Yeh, and Chien-Min Lin. 2020. "Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness" Cells 9, no. 8: 1859. https://doi.org/10.3390/cells9081859

APA Style

Su, Y.-K., Lin, J. W., Shih, J.-W., Chuang, H.-Y., Fong, I.-H., Yeh, C.-T., & Lin, C.-M. (2020). Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness. Cells, 9(8), 1859. https://doi.org/10.3390/cells9081859

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