Facilitation of Temozolomide Resistance of Glioblastoma by Long Noncoding RNA DLK1-35
PDF
HTML
EPub

Keywords

Delta-like non-canonical Notch ligand 1-35, Glioma, Temozolomide

Categories

How to Cite

Li, Y. ., Zheng, X. ., Li, D. ., Sun, M. ., Wang, Z. ., Li, J. ., & Li, Y. (2023). Facilitation of Temozolomide Resistance of Glioblastoma by Long Noncoding RNA DLK1-35. Iranian Red Crescent Medical Journal, 25(5). https://doi.org/10.32592/ircmj.2023.25.5.2468

Abstract

Background: Long noncoding RNAs played critical roles in glioblastoma development.

Objectives: This study aimed to examine the impacts of lncRNA DLK1-35 on glioblastoma cells and mice.

Methods: Methyl Thiazolyl Tetrazolium (MTT) was applied for examining the viabilities of U87 and U251 cells, as well as IC50 values of temozolomide (TMZ). LncRNA DLK1-35 expressions were detected using RT-qPCR. Proliferation and apoptosis of TMZ-resistant U251 (U251 TR) cells were evaluated using colony formation and flow cytometry, respectively. Western blot was applied to analyze O6-methylguanine-DNA methyltransferase (MGMT) protein expressions. The xenograft model was used for detecting the weight and volume of tumors in mice.

Results: TMZ treatment suppressed the viabilities of glioblastoma cells dose-dependently. Moreover, TMZ-resistant glioblastoma cells had higher IC50 values. lncRNA DLK1-35 was upregulated in TMZ-resistant cells while the suppression of lncRNA DLK1-35 caused low proliferation and a higher apoptosis rate. Moreover, MGMT was also inhibited by lncRNA DLK1-35 downregulation. Additionally, the weight and volume of tumors in mice were also inhibited with the knockdown of lncRNA DLK1-35.

Conclusion: Knockdown of lncRNA DLK1-35 inhibited MGMT to decrease the TMZ resistance in vitro and in vivo in glioblastoma.

https://doi.org/10.32592/ircmj.2023.25.5.2468
PDF
HTML
EPub

References

Huang B, Zhang H, Gu L, Ye B, Jian Z, Stary C, Xiong X.

Advances in immunotherapy for glioblastoma multiforme. J Immunol Res. 2017;2017:3597613. doi: 10.1155/2017/3597613. [PubMed: 28299344]

Wirsching HG, Weller M. Glioblastoma. Handb Clin Neurol. 2016;134:381-97. doi: 10.1016/B978-0-12-802997-8.00023-2. [PubMed: 26948367]

Arora A, Somasundaram K. Glioblastoma vs temozolomide: can the red queen race be won? Cancer Biol Ther. 2019;20(8):1083-90. doi: 10.1080/15384047.2019.1599662. [PubMed: 31068075]

Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M. Potential strategies overcoming the Temozolomide resistance for Glioblastoma. Neurol Med Chir. 2018,58(10):405-21. doi: 10.2176/nmc.ra.2018-0141. [PubMed: 30249919]

Kim MM, Umemura Y, Leung D. Bevacizumab and Glioblastoma: past, present, and future directions. Cancer J. 2018;24(4):180-6. doi: 10.1097/PPO.0000000000000326. [PubMed: 30119081]

Stevens MF, Hickman JA, Langdon SP, Chubb D, Vickers L, Stone R, et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res. 1987;47(22):5846-52. [PubMed: 3664486]

Davis ME. Epidemiology and overview of Gliomas. Semin Oncol Nurs. 2018;34(5):420-9. doi: 10.1016/j.soncn.2018.10.001. [PubMed: 30392758]

Xia Q, Liu L, Li Y, Zhang P, Han D, Dong L. Therapeutic perspective of temozolomide resistance in Glioblastoma treatment. Cancer Invest. 2021;39(8):627-44. doi: 10.2176/nmc.ra.2018-0141. [PubMed: 30249919]

Peng Y, Tang D, Zhao M, Kajiyama H, Kikkawa F, Kondo Y. Long non-coding RNA: A recently accentuated molecule in chemoresistance in cancer. Cancer Metastasis Rev. 2020;39(3):825-35. doi: 10.1007/s10555-020-09910-w. [PubMed: 32594276]

Sanchez Calle A, Kawamura Y, Yamamoto Y, Takeshita F, Ochiya T. Emerging roles of long non-coding RNA in cancer. Cancer Sci. 2018;109(7):2093-100. doi: 10.1111/cas.13642. [PubMed: 29774630]

Lu C, Wei Y, Wang X, Zhang Z, Yin J, Li W, et al. DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma. Mol Cancer. 2020;19(1):28. doi: 10.1186/s12943-020-1137-5. [PubMed: 32039732]

Qi J, Pan L, Yu Z, Ni W. The lncRNA RP3-439F8.1 promotes GBM cell proliferation and progression by sponging miR-139-5p to upregulate NR5A2. Pathol Res Pract. 2021;223:153319. doi: 10.1016/j.prp.2020.153319. [PMID: 33991848]

Zeng H, Xu N, Liu Y, Liu B, Yang Z, Fu Z, et al. Genomic profiling of long non-coding RNA and mRNA expression associated with acquired temozolomide resistance in glioblastoma cells. Int J Oncol. 2017;51(2):445-55. doi: 10.3892/ijo.2017.4033. [PubMed: 28714520]

DeSouza PA, Qu X, Chen H, Patel B, Maher CA, Kim AH.

Long, noncoding RNA dysregulation in Glioblastoma. Cancers. 2021;13(7):1604. doi: 10.3390/cancers13071604. [PubMed:33807183]

Shangguan W, Lv X, Tian N. FoxD2-AS1 is a prognostic factor in glioma and promotes temozolomide resistance in

a O(6)-methylguanine-DNA methyltransferase-dependent manner. Korean J Physiol Pharmacol. 2019;23(6):475-82. doi: 10.4196/kjpp.2019.23.6.475. [PubMed: 31680769]

Wu P, Cai J, Chen Q, Han B, Meng X, Li Y, et al. Lnc-TALC promotes O(6)-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p. Nat Commun. 2019;10(1):2045. doi: 10.1038/s41467-019-10025-2. [PubMed: 31053733]

Cai T, Liu Y, Xiao J. Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma. Cancer Med. 2018;7(4):1404-15. doi: 10.1002/cam4.1384. [PubMed: 29479863]

Lou J, Yan W, Li QY, Zhu AK, Tan BQ, Dong R, Zou XZ, Liu T. LncRNA MEG8 plays an oncogenic role in hepatocellular carcinoma progression through miR-367-3p/14-3-3ζ/TGFβR1 axis. Neoplasma. 2021;68(2):273-82.

Rao AM, Quddusi A, Shamim MS, The significance of MGMT methylation in Glioblastoma Multiforme prognosis. J Pak Med Assoc. 2018;68(7):1137-9. [PubMed: 30317322]

Lee SY. Temozolomide resistance in glioblastoma multiforme. Genes Dis. 2016;3(3):198-210. doi: 10.1016/j.gendis.2016.04.007. [PubMed: 30258889]