Abstract
Glioma is one type of primary intracranial carcinoma with a relatively poor prognosis. We investigated the level of SLC25A21-AS1 in gliomas and the association with survival and progression in patients with glioma. Specimens of gliomas from patients were assessed by quantitative real-time polymerase chain reaction analysis of the SLC25A21-AS1 level (117 specimens). For prognostic value assessment, χ2 test, Kaplan–Meier method with the log-rank test, and Multivariate survival analysis were performed. The direct targets for SLC25A21-AS1 were explored. The biological roles of SLC25A21-AS1 were investigated by manipulating the expression level of SLC25A21-AS1 in glioma cells. SLC25A21-AS1 was significantly downregulated in glioma specimens and cell lines compared to non-cancerous ones. Significant associations were found between SLC25A21-AS1 downregulation and WHO stage, IDH status, poor disease-free survival/overall survival. miR-221-3p/miR-222-3p were the target miRNAs for SLC25A21-AS1. Overexpression of SLC25A21-AS1 inhibited glioma cell growth, invasion, and migration while miR-221-3p/miR-222-3p-overexpressed groups could offset this effect. Downregulation of SLC25A21-AS1 in gliomas carries a universally poor prognosis. Overexpression of SLC25A21-AS1 inhibited glioma progression via miR-221-3p/miR-222-3p.
Similar content being viewed by others
References
Davis, M. E. (2018). Epidemiology and overview of gliomas. Seminars in Oncology Nursing., 34(5), 420–429.
Shinojima, N. (2021). Epidemiology for glioma. No shinkei geka Neurological Surgery, 49(3), 491–499.
Mandal, A. S., Romero-Garcia, R., Hart, M. G., & Suckling, J. (2020). Genetic, cellular, and connectomic characterization of the brain regions commonly plagued by glioma. Brain: A Journal of Neurology, 143(11), 3294–3307.
Perry, A., & Wesseling, P. (2016). Histologic classification of gliomas. Handbook of Clinical Neurology, 134, 71–95.
Mackintosh, C., Butterfield, R., Zhang, N., Lorence, J., Zlomanczuk, P., Bendok, B. R., et al. (2020). Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas. Neurologia i neurochirurgia polska, 54(5), 456–465.
Le Rhun, E., & Weller, M. (2020). Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours. ESMO Open, 5(Suppl 4), e001034.
Delgado-López, P. D., & Corrales-García, E. M. (2016). Survival in glioblastoma: A review on the impact of treatment modalities. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 18(11), 1062–1071.
Niu, X., Wang, T., Zhou, X., Yang, Y., Wang, X., Zhang, H., et al. (2020). Surgical treatment and survival outcome of patients with adult thalamic glioma: A single institution experience of 8 years. Journal of Neuro-oncology, 147(2), 377–386.
Felker, J., & Broniscer, A. (2020). Improving long-term survival in diffuse intrinsic pontine glioma. Expert Review of Neurotherapeutics, 20(7), 647–658.
Reifenberger, G., Wirsching, H. G., Knobbe-Thomsen, C. B., & Weller, M. (2017). Advances in the molecular genetics of gliomas—implications for classification and therapy. Nature Reviews Clinical Oncology, 14(7), 434–452.
Meng, X., Zhao, Y., Han, B., Zha, C., Zhang, Y., Li, Z., et al. (2020). Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways. Nature Communications, 11(1), 594.
Slack, F. J., & Chinnaiyan, A. M. (2019). The role of non-coding RNAs in oncology. Cell, 179(5), 1033–1055.
Yang, X., Liu, M., Li, M., Zhang, S., Hiju, H., Sun, J., et al. (2020). Epigenetic modulations of noncoding RNA: A novel dimension of cancer biology. Molecular Cancer, 19(1), 64.
Silva, A., Bullock, M., & Calin, G. (2015). The clinical relevance of long non-coding RNAs in cancer. Cancers, 7(4), 2169–2182.
Feng, Y., Wu, M., Hu, S., Peng, X., & Chen, F. (2020). LncRNA DDX11-AS1: A novel oncogene in human cancer. Human Cell, 33(4), 946–953.
Chan, J. J., & Tay, Y. (2018). Noncoding RNA:RNA regulatory networks in cancer. International Journal of Molecular Sciences, 19(5), 1310.
Wu, P., Cai, J., Chen, Q., Han, B., Meng, X., Li, Y., et al. (2019). Lnc-TALC promotes O(6)-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p. Nature Communications, 10(1), 2045.
Liu, Y., Wang, D., Ji, Q., & Yan, J. (2022). LncRNA MATN1-AS1 for prediction of prognosis in osteosarcoma patients and its cellular function. Molecular Biotechnology, 64(1), 66–74.
Tao, C., Luo, H., Chen, L., Li, J., Zhu, X., & Huang, K. (2021). Identification of an epithelial-mesenchymal transition related long non-coding RNA (LncRNA) signature in Glioma. Bioengineered, 12(1), 4016–4031.
Zheng, J., Zhou, Z., Qiu, Y., Wang, M., Yu, H., Wu, Z., et al. (2021). A prognostic ferroptosis-related lncRNAs signature associated with immune landscape and radiotherapy response in glioma. Frontiers in Cell and Developmental Biology, 9, 675555.
Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., et al. (2016). The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathologica, 131(6), 803–820.
Xi, J., Sun, Q., Ma, L., & Kang, J. (2018). Long non-coding RNAs in glioma progression. Cancer Letters, 419, 203–209.
Sasa, G. B. K, Xuan, C., Lyu, G., Ding, X., Meiyu, F. (2022). Long Non-coding RNA ZFPM2-AS1: A novel biomarker in the pathogenesis of human cancers. Molecular Biotechnology.
Torres-Bayona, S., Aldaz, P., Auzmendi-Iriarte, J., Saenz-Antoñanzas, A., Garcia, I., Arrazola, M., et al. (2018). PR-LncRNA signature regulates glioma cell activity through expression of SOX factors. Scientific Reports, 8(1), 12746.
Gong, X., Liao, X., & Huang, M. (2019). LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway. Pathology, Research and Practice, 215(3), 564–570.
Liu, H., Li, C., Yang, J., Sun, Y., Zhang, S., Yang, J., et al. (2018). Long noncoding RNA CASC9/miR-519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis. Journal of Cellular and Molecular Medicine, 22(12), 6338–6344.
Wang, S. J., Wang, H., Zhao, C. D., & Li, R. (2018). Long noncoding RNA LINC01426 promotes glioma progression through PI3K/AKT signaling pathway and serves as a prognostic biomarker. European Review for Medical and Pharmacological Sciences, 22(19), 6358–6368.
Zheng, Y., Lu, S., Xu, Y., & Zheng, J. (2019). Long non-coding RNA AGAP2-AS1 promotes the proliferation of glioma cells by sponging miR-15a/b-5p to upregulate the expression of HDGF and activating Wnt/β-catenin signaling pathway. International Journal of Biological Macromolecules, 128, 521–530.
Taniue, K., & Akimitsu, N. (2021). The functions and unique features of LncRNAs in cancer development and tumorigenesis. International Journal of Molecular Sciences., 22(2), 632.
Li, J., Liang, R., Song, C., Xiang, Y., & Liu, Y. (2020). Prognostic and clinicopathological significance of long non-coding RNA in glioma. Neurosurgical Review, 43(1), 1–8.
Li, Q., Wu, Q., Li, Z., Hu, Y., Zhou, F., Zhai, Z., et al. (2019). LncRNA LINC00319 is associated with tumorigenesis and poor prognosis in glioma. European Journal of Pharmacology., 861, 172556.
Shang, F., Du, S. W., & Ma, X. L. (2019). Up-regulation of lncRNA PXN-AS1-L is associated with unfavorable prognosis in patients suffering from glioma. European Review for Medical and Pharmacological Sciences, 23(20), 8950–8955.
Wang, X., Wang, C., Xu, H., & Xie, H. (2020). Long non-coding RNA SLC25A21-AS1 promotes multidrug resistance in nasopharyngeal carcinoma by regulating miR-324-3p/IL-6 axis. Cancer Management and Research, 12, 3949–3957.
Liang, Q., Li, X., Guan, G., Xu, X., Chen, C., Cheng, P., et al. (2019). Long non-coding RNA, HOTAIRM1, promotes glioma malignancy by forming a ceRNA network. Aging, 11(17), 6805–6838.
Dang, Y., Wei, X., Xue, L., Wen, F., Gu, J., & Zheng, H. (2018). Long non-coding RNA in glioma: Target miRNA and signaling pathways. Clinical Laboratory, 64(6), 887–894.
Sun, Y., Zhang, L., Wu, Q., Xu, C., Wang, P. (2022). Long noncoding RNA CRNDE functions as an oncogene to facilitate aggressive behaviors of nasopharyngeal carcinoma cells by modulating miR-3163/TWIST1 axis. Molecular Biotechnology, 64(4), 463–471.
Yang, F., Wang, W., Zhou, C., Xi, W., Yuan, L., Chen, X., et al. (2015). MiR-221/222 promote human glioma cell invasion and angiogenesis by targeting TIMP2. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine, 36(5), 3763–3773.
Xin, S., Huang, K., & Zhu, X. G. (2019). Non-coding RNAs: Regulators of glioma cell epithelial-mesenchymal transformation. Pathology, Research and Practice, 215(9), 152539.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
This study was approved by the Ethics Committee of the First Affiliated Hospital of Xiamen University.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Consent to publish
Patients signed informed consent regarding publishing their data.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhu, M., Li, K. & Zhang, J. Gliomas with Downregulation of lncRNA SLC25A21-AS1 Carry a Dismal Prognosis and an Accelerated Progression in Cell Proliferation, Migration and Invasion. Mol Biotechnol 64, 936–944 (2022). https://doi.org/10.1007/s12033-022-00472-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12033-022-00472-6