LncRNA CASC2 enhances sensitivity of glioma cells to temozolomide by ABCG2

Yanting LIU; Ran LUO; Yuefeng ZHU; Zhuangzhuang WANG; Wei GONG; Chunlei TIAN

doi:10.16016/j.1000-5404.202011207

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LncRNA CASC2 enhances sensitivity of glioma cells to temozolomide by ABCG2

更新时间：2026-01-09

- LncRNA CASC2 enhances sensitivity of glioma cells to temozolomide by ABCG2
- Journal of Third Military Medical University Vol. 43, Issue 10, Pages: 938-945(2021)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholar of China(81701278);the General Project of Hubei Provincial Health Commission(WJ2019M063);the Foundation of Medical and Health Research Projects of Yichang City(A18-301-03)
- DOI：10.16016/j.1000-5404.202011207
  CLC：
- Received：21 November 2020，
  
  Published：30 May 2021
- 稿件说明：
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Yanting LIU, Ran LUO, Yuefeng ZHU, et al. LncRNA CASC2 enhances sensitivity of glioma cells to temozolomide by ABCG2[J]. Journal of Third Military Medical University, 2021, 43(10): 938-945.
DOI：

Yanting LIU, Ran LUO, Yuefeng ZHU, et al. LncRNA CASC2 enhances sensitivity of glioma cells to temozolomide by ABCG2[J]. Journal of Third Military Medical University, 2021, 43(10): 938-945. DOI： 10.16016/j.1000-5404.202011207.

摘要

Abstract

Objective

To explore the effect of long noncoding RNA cancer susceptibility 2 (lncRNA CASC2) on the sensitivity of glioma cells to temazolamide (TMZ) and investigate the underling mechanism.

Methods

Forty glioma tissue samples derived from the 40 patients undergoing surgical treatment in our department from July 2018 to March 2020 were enrolled in this study. The expression of lncRNA CASC2 in the glioma tissues was detected with RT-PCR

and the results were analyzed with pathological grades and compared between the patients with isocitrate dehydrogenase (IDH) 1

/2 mutant (

=17) and IDH 1/2 wild type (

=9). Glioma cells U251 were cultured and transfected with plasmid pc-CASC2 to overexpress lncRNA CASC2 and/or interfering RNA of multi-drug resistance protein ABCG2. CCK-8 assay and flow cytometry were used to detect the cell viability and apoptotic rate in above cell groups after 30 μg/mL TMZ treatment. After mouse intracranial glioma model was established

high performance liquid chromatography was adopted to determine the concentration of TMZ. The correlation between lncRNA CASC2 and ABCG2 was detected by immunofluorescence staining and RNA immunoprecipitation.

Results

LncRNA CASC2 level was decreased in the glioma tissues with IDH 1/2 wild type

and had a negative correlation with pathological grade of glioma. LncRNA CASC2 overexpression resulted in significantly lower IC

to TMZ (36.7±4.2 μg/mL) than the U251 cells after pc-Null transfection (

=4.41

0.05). Under 30 μg/mL TMZ stimulation

the cell viability was reduced and the proportion of apoptotic cells was increased after lncRNA-CASC2 overexpression. In the mouse intracranial glioma model

the concentration of intracellular TMZ active product was increased after lncRNA-CASC2 overexpression. LncRNA CASC2 and ABCG2 were evenly distributed in the cytoplasm

and RNA immunoprecipitation showed that the content of lncRNA CASC2 in ABCG2 antibody group was higher than that in IgG control group. In addition

down-regulation of intracellular ABCG2 by siRNA decreased the TMZ sensitivity of U251 cells that could enhanced by lncRNA CASC2.

Conclusion

LncRNA CASC2 improves the sensitivity of glioma U251 cells to TMZ. However

ABCG2 inhibition by siRNA attenuates the above effects of lncRNA CASC2.

关键词

Keywords

references

顾润环朱尔春替莫唑胺联合放疗治疗恶性脑胶质瘤患者的临床研究中国临床药理学杂志 2020 36 10 1202 1204, 1227 https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ202010009.htm 顾润环, 朱尔春. 替莫唑胺联合放疗治疗恶性脑胶质瘤患者的临床研究[J]. 中国临床药理学杂志, 2020, 36(10): 1202-1204, 1227.

GU R H ZHU E C Clinical trial of temozolomide combined with radiotherapy in the treatment of patients with malignant glioma Chin J Clin Pharmacol 2020 36 10 1202 1204, 1227 https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ202010009.htm GU R H, ZHU E C. Clinical trial of temozolomide combined with radiotherapy in the treatment of patients with malignant glioma[J]. Chin J Clin Pharmacol, 2020, 36(10): 1202-1204, 1227.

BAHADUR S SAHU A K BAGHEL P Current promis- ing treatment strategy for glioblastoma multiform: a review Oncol Rev 2019 13 2 417 10.4081/oncol.2019.417 BAHADUR S, SAHU A K, BAGHEL P, et al . Current promis- ing treatment strategy for glioblastoma multiform: a review[J ] . Oncol Rev, 2019, 13(2): 417. DOI: 10.4081/oncol.2019.417.

DEGOOIJER M C DE VRIES N A BUCKLE T Improved brain penetration and antitumor efficacy of temozolomide by inhibition of ABCB 1 and ABCG2 Neoplasia 2018 20 7 710 720 10.1016/j.neo.2018.05.001 DEGOOIJER M C, DE VRIES N A, BUCKLE T, et al . Improved brain penetration and antitumor efficacy of temozolomide by inhibition of ABCB 1 and ABCG2[J ] . Neoplasia, 2018, 20(7): 710-720. DOI: 10.1016/j.neo.2018.05.001.

KIM S S HARFORD J B MOGHE M Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide Nucleic Acids Res 2018 46 3 1424 1440 10.1093/nar/gkx1221 KIM S S, HARFORD J B, MOGHE M, et al . Targeted nanocomplex carrying siRNA against MALAT1 sensitizes glioblastoma to temozolomide[J ] . Nucleic Acids Res, 2018, 46(3): 1424-1440. DOI: 10.1093/nar/gkx1221.

ZHANG J CHEN G GAO Y HOTAIR/miR-125 axis-mediated Hexokinase 2 expression promotes chemoresistance in human glioblastoma J Cell Mol Med 2020 24 10 5707 5717 10.1111/jcmm.15233 ZHANG J, CHEN G, GAO Y, et al . HOTAIR/miR-125 axis-mediated Hexokinase 2 expression promotes chemoresistance in human glioblastoma[J ] . J Cell Mol Med, 2020, 24(10): 5707-5717. DOI: 10.1111/jcmm.15233.

YU L CHEN S BAO H The role of lncRNA CASC 2 on prognosis of malignant tumors: a meta-analysis and bio-informatics OncoTargets Ther 2018 11 4355 4365 10.2147/ott.s166132 YU L, CHEN S, BAO H, et al . The role of lncRNA CASC 2 on prognosis of malignant tumors: a meta-analysis and bio-informatics[J ] . OncoTargets Ther, 2018, 11: 4355-4365. DOI: 10.2147/ott.s166132.

LEE S Y Temozolomide resistance in glioblastoma multiforme Genes Dis 2016 3 3 198 210 10.1016/j.gendis.2016.04.007 LEE S Y. Temozolomide resistance in glioblastoma multiforme[J]. Genes Dis, 2016, 3(3): 198-210. DOI: 10.1016/j.gendis.2016.04.007.

JIAPAER S FURUTA T TANAKA S Potential strategies overcoming the temozolomide resistance for glioblastoma Neurol Med Chir (Tokyo) 2018 58 10 405 421 10.2176/nmc.ra.2018-0141 JIAPAER S, FURUTA T, TANAKA S, et al . Potential strategies overcoming the temozolomide resistance for glioblastoma[J ] . Neurol Med Chir (Tokyo), 2018, 58(10): 405-421. DOI: 10.2176/nmc.ra.2018-0141.

DANIEL P SABRI S CHADDAD A Temozolomide induced hypermutation in glioma: evolutionary mechanisms and therapeutic opportunities Front Oncol 2019 9 41 10.3389/fonc.2019.00041 DANIEL P, SABRI S, CHADDAD A, et al . Temozolomide induced hypermutation in glioma: evolutionary mechanisms and therapeutic opportunities[J ] . Front Oncol, 2019, 9: 41. DOI: 10.3389/fonc.2019.00041.

NI W XIA Y X BI Y X FoxD2-AS1 promotes glioma progression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway Aging 2019 11 5 1427 1439 10.18632/aging.101843 NI W, XIA Y X, BI Y X, et al . FoxD2-AS1 promotes glioma prog ression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway[J ] . Aging, 2019, 11(5): 1427-1439. DOI: 10.18632/aging.101843.

JIA L TIAN Y CHEN Y The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/β-Catenin pathway OncoTargets Ther 2018 11 313 321 10.2147/ott.s154339 JIA L, TIAN Y, CHEN Y, et al . The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/β-Catenin pathway[J ] . OncoTargets Ther, 2018, 11: 313-321. DOI: 10.2147/ott.s154339.

WANG J JIA J ZHOU L Long non-coding RNACASC 2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK 1 axis Neoplasma 2020 67 6 1279 1292 10.4149/neo_2020_191029N1102 WANG J, JIA J, ZHOU L. Long non-codi ng RNACASC 2 enhances cisplatin sensitivity in oral squamous cell cancer cells by the miR-31-5p/KANK 1 axis[J ] . Neoplasma, 2020, 67(6): 1279-1292. DOI: 10.4149/neo_2020_191029N1102.

FENG Y ZOU W HU C Modulation of CASC 2 /miR-21/PTEN pathway sensitizes cervical cancer to cisplatin Arch Biochem Biophys 2017 623/624 20 30 10.1016/j.abb.2017.05.001 FENG Y, ZOU W, HU C, et al . Modulation of CASC 2 /miR-21/PTEN pathway sensitizes cervical cancer to cisplatin[J ] . Arch Biochem Biophys, 2017, 623/624: 20-30. DOI: 10.1016/j.abb.2017.05.001.

FANG Y FULLWOOD M J Roles, functions, and mechanisms of long non-coding RNAs in cancer Genom Proteom Bioinf 2016 14 1 42 54 10.1016/j.gpb.2015.09.006 FANG Y, FULLWOOD M J. Roles, functions, and mechanisms of long non-coding RNAs in cancer[J]. Genom Proteom Bioinf, 2016, 14(1): 42-54. DOI: 10.1016/j.gpb.2015.09.006.

LI Z Z ZHANG J X ZHENG H S Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme J Exp Clin Cancer Res 2019 38 1 380 10.1186/s13046-019-1371-0 LI Z Z, ZHANG J X, ZHENG H S, et al . Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib, overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme[J ] . J Exp Clin Cancer Res, 2019, 38(1): 380. DOI: 10.1186/s13046-019-1371-0.

YAN Y XU Z CHEN X Novel function of lncRNA ADAMTS9-AS2 in promoting temozolomide resistance in glioblastoma via upregulating the FUS/MDM2 ubiquitination axis Front Cell Dev Biol 2019 2 7 217 226 10.3389/fcell.2019.00217 YAN Y, XU Z, CHEN X, et al . Novel function of lncRNA ADAMTS9-AS2 in promoting temozolomide resistance in glioblastoma via upregulating the FUS/MDM2 ubiquitination axis[J ] . Front Cell Dev Biol, 2019, 2(7): 217-226. DOI: 10.3389/fcell.2019.00217.

LIU B ZHOU J WANG C LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH 5 -mediated epigenetic regulation in glioblastoma Cell Death Dis 2020 11 5 384 10.1038/s41419-020-2540-y LIU B, ZHOU J, WANG C, et al . LncRNA SOX2OT promotes temozolomide resistance by elevating SOX2 expression via ALKBH 5 -mediated epigenetic regulation in glioblastoma[J ] . Cell Death Dis, 2020, 11(5): 384. DOI: 10.1038/s41419-020-2540-y.

LIN F DEGOOIJER M C ROIG E M ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy Clin Cancer Res 2014 20 10 2703 2713 10.1158/1078-0432.ccr-14-0084 LIN F, DEGOOIJER M C, ROIG E M, et al . ABCB1, ABCG2, and PTEN determine the response of glioblastoma to temozolomide and ABT-888 therapy[J ] . Clin Cancer Res, 2014, 20(10): 2703-2713. DOI: 10.1158/1078-0432.ccr-14-0084.

LIU X CHEN J LI W Inhibition of casein kinase Ⅱ by CX-4945, but not yes-associated protein (YAP) by verteporfin, enhances the antitumor efficacy of temozolomide in glioblastoma Transl Oncol 2020 13 1 70 78 10.1016/j.tranon.2019.09.006 LIU X, CHEN J, LI W, et al . Inhibition of casein kinase Ⅱ by CX-4945, but not yes-associated protein (YAP) by verteporfin, enhances the antitumor efficacy of temozolomide in glioblastoma[J ] . Transl Oncol, 2020, 13(1): 70-78. DOI: 10.1016/j.tranon.2019.09.006.

LIU B GUO Z DONG H LRIG1, human EGFR inhibitor, reverses multidrug resistance through modulation of ABCB1 and ABCG2 Brain Res 2015 1611 93 100 10.1016/j.brainres.2015.03.023.Epub2015Mar20 LIU B, GUO Z, DONG H, et al . LRIG1, human EGFR inhibitor, reverses multidrug resistance through modulation of ABCB1 and ABCG2[J ] . Brain Res. 2015, 1611: 93-100. DOI: 10.1016/j.brainres.2015.03.023.Epub 2015 Mar 20.

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