Abstract
Glioblastoma (GBM) is a highly aggressive and lethal brain tumor, and despite conventional treatments, patient prognosis remains poor. Understanding the molecular mechanisms driving GBM and identifying potential therapeutic targets is critical. MOV10, an RNA helicase, is overexpressed in multiple cancers and is considered an oncogene. Our analysis of datasets from TCGA, GEO, and CGGA showed that MOV10 expression is elevated in GBM and strongly negatively correlated with overall survival (OS). Cox regression confirmed MOV10 as an independent prognostic risk factor for GBM.Functional enrichment analysis revealed that MOV10 is involved in immune regulation and tumor progression pathways. We found that MOV10 expression is closely linked to immune infiltration, immune checkpoint expression, and responses to immunotherapy. Immunofluorescence and Transwell assays confirmed that MOV10 knockdown reduced M2 macrophage migration and invasion in GBM cells. Clinical analysis further validated MOV10 overexpression in GBM tissues.In vitro, MOV10 silencing suppressed GBM cell proliferation, inhibited EMT-like processes, and promoted apoptosis through autophagy modulation. Our findings suggest that MOV10 plays a crucial role in GBM progression and could be a promising molecular target for therapy.
Similar content being viewed by others
Data availability
The datasets generated and/or analyzed during the current study are available in the [CGGA] repository [https://www.cgga.org.cn]; the [UCSC] repository [https://xenabrowser.net/datapages]; the [cbioportal] repository [https://www.cbioportal.org]; and the [TIDE] repository [http://tide.dfci.harvard.edu]. These datasets are all public datasets. Other datasets used in the current study are noted in the Methods section. We will provide some code for your publication if you require code reproduction.The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
References
Aldape, K. et al. Challenges to curing primary brain tumours[J]. Nat. Rev. Clin. Oncol. 16 (8), 509–520 (2019).
Zhang, L. et al. The utility of diffusion MRI with quantitative ADC measurements for differentiating high-grade from low-grade cerebral gliomas: evidence from a meta-analysis[J]. J. Neurol. Sci. 373, 9–15 (2017).
Chen, R. et al. Glioma subclassifications and their clinical Significance[J]. Neurotherapeutics 14 (2), 284–297 (2017).
Ostrom, Q. T. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2016–2020. Neuro Oncol. 25 (12 Suppl 2), iv1–iv99 (2023).
Chen, J. et al. A restricted cell population propagates glioblastoma growth after chemotherapy[J]. Nature 488 (7412), 522–526 (2012).
Gregersen, L. H. et al. MOV10 is a 5’ to 3’ RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3’ UTRs[J]. Mol. Cell. 54 (4), 573–585 (2014).
Li, S. et al. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production[J]. Immunity 35 (3), 426–440 (2011).
Nawaz, A. et al. Unwinding the roles of RNA helicase MOV10[J]. Wiley Interdiscip Rev. RNA. 13 (2), e1682 (2022).
Fairman-Williams, M. E., Guenther, U. P. & Jankowsky, E. SF1 and SF2 helicases: family matters[J]. Curr. Opin. Struct. Biol. 20 (3), 313–324 (2010).
Nakano, M. et al. MOV10 as a novel telomerase-associated protein[J]. Biochem. Biophys. Res. Commun. 388 (2), 328–332 (2009).
Yang, D. et al. MiR-760 enhances sensitivity of pancreatic cancer cells to gemcitabine through modulating integrin beta1[J]. Biosci Rep, 39 (11), BSR20192358. (2019).
He, Q. et al. MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change[J]. J. Exp. Clin. Cancer Res. 38 (1), 9 (2019).
Gangoso, E. et al. Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion[J]. Cell 184 (9), 2454–2470 (2021).
Zhang, Y. & Zhang, Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications[J]. Cell. Mol. Immunol. 17 (8), 807–821 (2020).
Morales, E. et al. Role of immunotherapy in ewing sarcoma[J]. J Immunother Cancer, 8 (2), e000653 (2020).
Alban, T. J. et al. Glioblastoma Myeloid-Derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune Suppression[J]. Front. Immunol. 11, 1191 (2020).
Goodier, J. L., Cheung, L. E. & Kazazian, H. J. MOV10 RNA helicase is a potent inhibitor of Retrotransposition in cells[J]. PLoS Genet. 8 (10), e1002941 (2012).
Song, Z. W. et al. Altered mRNA levels of MOV10, A3G, and IFN-alpha in patients with chronic hepatitis B[J]. J. Microbiol. 52 (6), 510–514 (2014).
Jung, H., Choi, J. K. & Lee, E. A. Immune signatures correlate with L1 Retrotransposition in Gastrointestinal cancers[J]. Genome Res. 28 (8), 1136–1146 (2018).
Gruntman, A. M. & Flotte, T. R. The rapidly evolving state of gene therapy[J]. FASEB J. 32 (4), 1733–1740 (2018).
Xin, Y. et al. Nano-based delivery of RNAi in cancer therapy[J]. Mol. Cancer. 16 (1), 134 (2017).
El, M. S. et al. Role for the MOV10 RNA helicase in polycomb-mediated repression of the INK4a tumor suppressor[J]. Nat. Struct. Mol. Biol. 17 (7), 862–868 (2010).
Mao, C. G. et al. BCAR1 promotes proliferation and cell growth in lung adenocarcinoma via upregulation of POLR2A[J]. Thorac. Cancer. 11 (11), 3326–3336 (2020).
Turkalp, Z., Karamchandani, J. & Das, S. IDH mutation in glioma: new insights and promises for the future[J]. JAMA Neurol. 71 (10), 1319–1325 (2014).
Gao, F. et al. CIP2A mediates fibronectin-induced bladder cancer cell proliferation by stabilizing beta-catenin[J]. J. Exp. Clin. Cancer Res. 36 (1), 70 (2017).
Ingham, M. & Schwartz, G. K. Cell-Cycle therapeutics come of Age[J]. J. Clin. Oncol. 35 (25), 2949–2959 (2017).
Pastushenko, I. & Blanpain, C. EMT transition States during tumor progression and Metastasis[J]. Trends Cell. Biol. 29 (3), 212–226 (2019).
Cho, E. S. et al. Therapeutic implications of cancer epithelial-mesenchymal transition (EMT)[J]. Arch. Pharm. Res. 42 (1), 14–24 (2019).
Wang, W. et al. Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production[J]. Oncogenesis 4, e154 (2015).
Ostroumov, D. et al. CD4 and CD8 T lymphocyte interplay in controlling tumor growth[J]. Cell. Mol. Life Sci. 75 (4), 689–713 (2018).
Dolina, J. S. et al. CD8(+) T cell exhaustion in Cancer[J]. Front. Immunol. 12, 715234 (2021).
Kim, H. J. & Cantor, H. CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful[J]. Cancer Immunol. Res. 2 (2), 91–98 (2014).
Sadri, M. et al. Potential applications of macrophages in cancer immunotherapy. Biomed. Pharmacother. 178, 117161 (2024).
Najafi, M. et al. Macrophage Polarity in cancer: A review. J. Cell. Biochem. 120 (3), 2756–2765 (2019).
Li, B., Chan, H. L. & Chen, P. Immune checkpoint inhibitors: basics and Challenges[J]. Curr. Med. Chem. 26 (17), 3009–3025 (2019).
Kouidhi, S., Ben, A. F. & Benammar, E. A. Targeting tumor metabolism: A new challenge to improve Immunotherapy[J]. Front. Immunol. 9, 353 (2018).
Morad, G. et al. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade[J]. Cell 184 (21), 5309–5337 (2021).
Rizvi, N. A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 Blockade in non-small cell lung cancer[J]. Science 348 (6230), 124–128 (2015).
Hill, B. S. et al. Recruitment of stromal cells into tumour microenvironment promote the metastatic spread of breast cancer[J]. Semin Cancer Biol. 60, 202–213 (2020).
Zhan, H. X. et al. Crosstalk between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology[J]. Cancer Lett. 392, 83–93 (2017).
Clavreul, A. & Menei, P. Mesenchymal Stromal-Like cells in the glioma microenvironment: what are these cells?[J]. Cancers (Basel), 12 (9), 2628 (2020).
Galluzzi, L. et al. Autophagy in malignant transformation and cancer progression[J]. EMBO J. 34 (7), 856–880 (2015).
Amaravadi, R., Kimmelman, A. C. & White, E. Recent insights into the function of autophagy in cancer[J]. Genes Dev. 30 (17), 1913–1930 (2016).
Towers, C. G. & Thorburn, A. Therapeutic Target. Autophagy[J] EBioMedicine, 14: 15–23. (2016).
Wang, D. et al. The role of NLRP3-CASP1 in inflammasome-mediated neuroinflammation and autophagy dysfunction in manganese-induced, hippocampal-dependent impairment of learning and memory ability[J]. Autophagy 13 (5), 914–927 (2017).
Meng, L. et al. Prognostic autophagy model based on CASP4 and BIRC5 expression in patients with renal cancer: independent datasets-based study[J]. Am. J. Transl Res. 12 (11), 7475–7489 (2020).
Allavena, G. et al. Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation[J]. Autophagy 14 (2), 252–268 (2018).
Sung, J. S. et al. ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts[J]. Oncogene 39 (3), 664–676 (2020).
Kozako, T. et al. High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor[J]. Eur. J. Pharmacol. 865, 172738 (2019).
Xu, J. et al. A prognostic model for colon cancer patients based on eight signature autophagy Genes[J]. Front. Cell. Dev. Biol. 8, 602174 (2020).
Marsh, T. & Debnath, J. Autophagy suppresses breast cancer metastasis by degrading NBR1[J]. Autophagy 16 (6), 1164–1165 (2020).
Meyer, N. et al. Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death[J]. Autophagy 17 (11), 3424–3443 (2021).
Huang, T. et al. Cannabidiol inhibits human glioma by induction of lethal mitophagy through activating TRPV4[J]. Autophagy 17 (11), 3592–3606 (2021).
Pistritto, G. et al. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies[J]. Aging (Albany NY). 8 (4), 603–619 (2016).
Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation[J]. Nucleic Acids Res. 44, D457–D462 (2016).
Zhang, H. et al. Optimized dynamic network biomarker Deciphers a High-Resolution heterogeneity within thyroid cancer molecular Subtypes[J]. Med Research : n. pag. (2025).
Funding
This work was supported by the National Natural Science Foundation of China (82360736), Jiangxi Province Ganpo Elite Talent Program – Innovative High-Level Talent Project (Medical and Health Category, Young Talent, gpyc20250235).The Distinguished Young Scholars program of the Natural Science Foundation of Jiangxi Province (20224ACB216015). Natural Science Foundation of Jiangxi Province（20252BAC240047)，Key Project of the Science and Technology Research Program of the Jiangxi Provincial Department of Education（GJJ2503418)，Youth Project of the Science and Technology Program of the Jiangxi Provincial Health Commission（202610077)，Open Research Fund of Jiangxi Cancer Hospital & Institute (KFJJ2023ZD05), The"Five-level Progressive" talent cultivation project of Jiangxi Cancer Hospital & Institute (WCDJ2024YQ03).
Author information
Authors and Affiliations
Contributions
Shuhui Chen: Project administration, Methodology, Formal analysis, Conceptualization. Linlin Ruan: Methodology, Formal analysis, Conceptualization. Feiyu Wang: Writing – original draft. Wenbin Yang: Methodology. Yueben Hu: Writing – review & editing. Yangzhon Guo: Methodology. Xuanxuan Xiong: Methodology. Dan Liu: Writing – review & editing, Validation. Qiaoli Lv: Writing – review & editing, Validation, Conceptualization.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Jiangxi Cancer Hospital (2020ky008).
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Wang, F., Ruan, L., Yang, W. et al. MOV10, a novel immunotherapy and prognostic biomarker, contributes to glioma development by regulating autophagy. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40396-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-40396-8
