GC-05. Long non-coding RNAs as potential targets for genome editing and gene therapy
Anton S. Dome, Dmitry V. Semenov, Grigory A. Stepanov
Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
Anton S. Dome, phone: +7 (953) 876-97-17, e-mail: firstname.lastname@example.org
The development of genome editing methods and the discovery of the RfxCas13d endonuclease (CasRx) allow to target not only protein-coding genes but also non-coding RNAs. Regulators of the processes of transcription and translation, long noncoding RNAs (lncRNAs) become promising targets for gene therapy. Glioblastoma is one of the oncological diseases, which develop involving lncRNAs. An incomplete understanding of the pathogenesis of glioblastoma makes it difficult to develop an effective therapy. The study of pathogenesis is usually carried out on model cell lines. The models of glioblastoma are the cell lines U87MG, U251MG, U343MG.
Materials and methods
In this work, bioinformatic analysis of the transcriptomic data of the cell lines U87MG, U251MG, and U343MG was carried out in comparison with the lines WI-38, HEK293FT, HEB, BEAS2B, IMR90.
Based on the data of current analysis, three lncRNA have an increased level of expression in glioma lines compared to the group of control cell lines and were selected as potential targets. A high level of LINC00461 is observed in glioma cell lines  and in patients with multiple myeloma . LINC01152 is localized mainly in the nucleus and is involved both in the regulation of gene transcription, in particular, IL-23 , and in post-transcriptional regulation, for example, by interacting with the 3’-UTR of MAML2 . In glioblastoma, increased expression of LINC01152 promotes epithelial-mesenchymal transition (EMT) . It is shown that LINC01272 also promotes EMT in gastric and colorectal cancer .
Using the CasRx system, we will get and characterize cell lines with knockdown of selected lncRNAs. This will allow a deeper study of the role of the selected targets in oncogenesis, as well as improve the strategy of finding and suppressing target genes for gene therapy of oncology.
This work was carried out with the support of the Russian Science Foundation (project No. 21-14-00195), as well as with partial support of the project of basic budgetary financing of the Ministry of Education and Science of the Russian Federation (0245-2019-0001).
1. Yang Y. et al. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget. 2017; 8(48): 84123.
2. Deng M. et al. Exosome-transmitted LINC00461 promotes multiple myeloma cell proliferation and suppresses apoptosis by modulating microRNA/BCL-2 expression. Cytotherapy. 2019; 21(1): 96-106.
3. Chen T. et al. HBx-related long non-coding RNA 01152 promotes cell proliferation and survival by IL-23 in hepatocellular carcinoma. Biomedicine & Pharmacotherapy. 2019;115:108877.
4. Wu J. et al. LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway. Cell death & disease. 2021; 12(1):1-14.
5. Chang L. et al. LncRNA RP11-84E24. 3 drives tumorigenesis and epithelial-to-mesenchymal transition of glioma cells by promoting TFAP2C-mediated activation of SNAI1. J. Neuro-Oncol. 2021; 151(2): 157-171.
6. Leng X. et al. LINC01272 promotes migration and invasion of gastric cancer cells via EMT. OncoTargets and Therapy. 2020; 13:3401.
CasRx, lncRNA, glioblastoma.