nach oben

Acta Neurologica Belgica

Erschienen in:

19.04.2023 | Original article

FXR1 promotes glioma progression by downregulating microRNA-124-3p through long noncoding RNA FGD5-AS1 upregulation

verfasst von: Xin Gong, Mengyi Huang, Lei Chen, Huan Zeng

Erschienen in: Acta Neurologica Belgica | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

Abstract

Objective

As reported, glioma progression is affected by altered FXR1, long non-coding RNA FGD5-AS1, and microRNA (miR)-124-3p. However, relationships among these genes remain unclear. Accordingly, this paper ascertains whether FXR1 manipulates glioma progression via the FGD5-AS1/miR-124-3p axis.

Methods

Glioma tissues were harvested, in which FGD5-AS1 and miR-124-3p levels were examined with qRT-PCR and FXR1 level was assessed with qRT-PCR and western blot. The interaction of miR-124-3p with FGD5-AS1 was analyzed by dual-luciferase reporter, RIP, and Pearson correlation coefficient assays, and that of FXR1 with FGD5-AS1 was assessed by RIP and Pearson correlation coefficient assays. Glioma cells were obtained, followed by qRT-PCR detection of miR-124-3p expression. After gain- or loss-of-function assays, EdU, Transwell, and tubule formation assays were performed to determine cell proliferation, invasion and migration, and angiogenesis. Next, the intracranial in situ graft tumor model was established for in vivo verification.

Results

FGD5-AS1 and FXR1 levels were high, but miR-124-3p level was low in glioma tissues. Likewise, glioma cells had downregulated miR-124-3p expression. Mechanistically, FGD5-AS1 negatively bound to miR-124-3p, and FXR1 was positively correlated and interacted with FGD5-AS1. miR-124-3p overexpression or FGD5-AS1 or FXR1 knockdown restricted cell invasion, proliferation, migration, and angiogenesis in gliomas. miR-124-3p inhibition abrogated the repressive impacts of FXR1 knockdown on the malignant progression of gliomas. Also, FXR1 constrained tumor growth and angiogenesis in mice, which was counterweighed by inhibiting miR-124-3p.

Conclusion

FXR1 might act as an oncogene in gliomas by declining miR-124-3p through FGD5-AS1.

Nur mit Berechtigung zugänglich

Li D, Patel CB, Xu G, Iagaru A, Zhu Z, Zhang L et al (2020) Visualization of diagnostic and therapeutic targets in glioma with molecular imaging. Front Immunol 11:592389. https://doi.org/10.3389/fimmu.2020.592389CrossRefPubMedPubMedCentral

Ludwig K, Kornblum HI (2017) Molecular markers in glioma. J Neurooncol 134(3):505–512. https://doi.org/10.1007/s11060-017-2379-yCrossRefPubMedPubMedCentral

Berger TR, Wen PY, Lang-Orsini M, Chukwueke UN (2022) World Health Organization 2021 classification of central nervous system tumors and implications for therapy for adult-type gliomas: a review. JAMA Oncol 8(10):1493–1501. https://doi.org/10.1001/jamaoncol.2022.2844CrossRefPubMed

Yang K, Wu Z, Zhang H, Zhang N, Wu W, Wang Z et al (2022) Glioma targeted therapy: insight into future of molecular approaches. Mol Cancer 21(1):39. https://doi.org/10.1186/s12943-022-01513-zCrossRefPubMedPubMedCentral

Alfonso JCL, Talkenberger K, Seifert M, Klink B, Hawkins-Daarud A, Swanson KR et al (2017) The biology and mathematical modelling of glioma invasion: a review. J R Soc Interface 14:136. https://doi.org/10.1098/rsif.2017.0490CrossRef

Miyauchi JT, Tsirka SE (2018) Advances in immunotherapeutic research for glioma therapy. J Neurol 265(4):741–756. https://doi.org/10.1007/s00415-017-8695-5CrossRefPubMed

Sun J, Ma Q, Shu C, Xiong J, Li B, Wu J et al (2021) MicroRNA301a/ZNRF3/wnt/betacatenin signal regulatory crosstalk mediates glioma progression. Int J Oncol 58(1):45–56. https://doi.org/10.3892/ijo.2020.5145CrossRefPubMed

Zhou Q, Liu J, Quan J, Liu W, Tan H, Li W (2018) MicroRNAs as potential biomarkers for the diagnosis of glioma: a systematic review and meta-analysis. Cancer Sci 109(9):2651–2659. https://doi.org/10.1111/cas.13714CrossRefPubMedPubMedCentral

Zhang G, Xia M, Guo J, Huang Y, Huang J, Wei K et al (2021) microRNA-1296 inhibits glioma cell growth by targeting ABL2. Technol Cancer Res Treat 20:1533033821990009. https://doi.org/10.1177/1533033821990009CrossRefPubMedPubMedCentral

10.

Pan DS, Cao P, Li JJ, Fan D, Song ZQ (2019) MicroRNA-374b inhibits migration and invasion of glioma cells by targeting EGFR. Eur Rev Med Pharmacol Sci 23(10):4254–4263. https://doi.org/10.26355/eurrev_201905_17930CrossRefPubMed

11.

Lv Z, Zhao Y (2017) MiR-124 inhibits cell proliferation, invasion, and migration in glioma by targeting Smad2. Int J Clin Exp Pathol 10(11):11369–11376PubMedPubMedCentral

12.

Wang R, Zhang S, Chen X, Li N, Li J, Jia R et al (2018) EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Mol Cancer 17(1):166. https://doi.org/10.1186/s12943-018-0911-0CrossRefPubMedPubMedCentral

13.

Wu Q, Zhong H, Jiao L, Wen Y, Zhou Y, Zhou J et al (2020) MiR-124–3p inhibits the migration and invasion of gastric cancer by targeting ITGB3. Pathol Res Pract 216(1):152762. https://doi.org/10.1016/j.prp.2019.152762CrossRefPubMed

14.

Li Y, Wang X, Zhao Z, Shang J, Li G, Zhang R (2021) LncRNA NEAT1 promotes glioma cancer progression via regulation of miR-98-5p/BZW1. Biosci Rep. https://doi.org/10.1042/BSR20200767

15.

Wang WJ, Sun K, Li FY, Hui XB, Liu D, Liu J et al (2020) LncRNA HANR aggravates the malignant progression of glioma via targeting miRNA-335. Eur Rev Med Pharmacol Sci 24(2):758–765. https://doi.org/10.26355/eurrev_202001_20056CrossRefPubMed

16.

Lin JZ, Lin N, Zhao WJ (2020) Identification and validation of a six-lncRNA prognostic signature with its ceRNA networks and candidate drugs in lower-grade gliomas. Genomics 112(5):2990–3002. https://doi.org/10.1016/j.ygeno.2020.05.016CrossRefPubMed

17.

He Z, Ruan X, Liu X, Zheng J, Liu Y, Liu L et al (2019) FUS/circ_002136/miR-138-5p/SOX13 feedback loop regulates angiogenesis in Glioma. J Exp Clin Cancer Res 38(1):65. https://doi.org/10.1186/s13046-019-1065-7CrossRefPubMedPubMedCentral

18.

Cao S, Zheng J, Liu X, Liu Y, Ruan X, Ma J et al (2019) FXR1 promotes the malignant biological behavior of glioma cells via stabilizing MIR17HG. J Exp Clin Cancer Res 38(1):37. https://doi.org/10.1186/s13046-018-0991-0CrossRefPubMedPubMedCentral

19.

Liang H, Ge F, Xu Y, Xiao J, Zhou Z, Liu R et al (2018) miR-153 inhibits the migration and the tube formation of endothelial cells by blocking the paracrine of angiopoietin 1 in breast cancer cells. Angiogenesis 21(4):849–860. https://doi.org/10.1007/s10456-018-9630-9CrossRefPubMedPubMedCentral

20.

Yang C, Zheng J, Xue Y, Yu H, Liu X, Ma J et al (2017) The effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 axis regulating glioblastoma angiogenesis. Front Mol Neurosci 10:437. https://doi.org/10.3389/fnmol.2017.00437CrossRefPubMed

21.

Xu Y, Zhang H, Sun Q, Geng R, Yuan F, Liu B et al (2021) Immunomodulatory effects of tryptophan metabolism in the glioma tumor microenvironment. Front Immunol 12:730289. https://doi.org/10.3389/fimmu.2021.730289CrossRefPubMedPubMedCentral

22.

Yang L, Xu X, Zheng J (2020) Microtubule-associated protein 2 knockdown sensitizes glioma cells to vincristine treatment. NeuroReport 31(3):197–204. https://doi.org/10.1097/WNR.0000000000001378CrossRefPubMed

23.

Fu W, Wu X, Yang Z, Mi H (2019) The effect of miR-124-3p on cell proliferation and apoptosis in bladder cancer by targeting EDNRB. Arch Med Sci 15(5):1154–1162. https://doi.org/10.5114/aoms.2018.78743CrossRefPubMed

24.

Liu F, Hu H, Zhao J, Zhang Z, Ai X, Tang L et al (2018) miR-124-3p acts as a potential marker and suppresses tumor growth in gastric cancer. Biomed Rep 9(2):147–155. https://doi.org/10.3892/br.2018.1113CrossRefPubMedPubMedCentral

25.

Wang Y, Chen L, Wu Z, Wang M, Jin F, Wang N et al (2016) miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL. BMC Cancer 16(1):826. https://doi.org/10.1186/s12885-016-2862-4CrossRefPubMedPubMedCentral

26.

Song Y, Bai L, Yan F, Chen C (2021) Inhibition of EMMPRIN by microRNA-124 suppresses the growth, invasion and tumorigenicity of gliomas. Exp Ther Med 22(3):930. https://doi.org/10.3892/etm.2021.10362CrossRefPubMedPubMedCentral

27.

Liu Z, Guo S, Sun H, Bai Y, Song Z, Liu X (2020) Circular RNA CircHIPK3 elevates CCND2 expression and promotes cell proliferation and invasion through miR-124 in glioma. Front Genet 11:1013. https://doi.org/10.3389/fgene.2020.01013CrossRefPubMedPubMedCentral

28.

Deng D, Luo K, Liu H, Nie X, Xue L, Wang R et al (2019) p62 acts as an oncogene and is targeted by miR-124-3p in glioma. Cancer Cell Int 19:280. https://doi.org/10.1186/s12935-019-1004-xCrossRefPubMedPubMedCentral

29.

Zhang G, Chen L, Khan AA, Li B, Gu B, Lin F et al (2018) miRNA-124-3p/neuropilin-1(NRP-1) axis plays an important role in mediating glioblastoma growth and angiogenesis. Int J Cancer 143(3):635–644. https://doi.org/10.1002/ijc.31329CrossRefPubMed

30.

Venkatesh J, Wasson MD, Brown JM, Fernando W, Marcato P (2021) LncRNA-miRNA axes in breast cancer: novel points of interaction for strategic attack. Cancer Lett 509:81–88. https://doi.org/10.1016/j.canlet.2021.04.002CrossRefPubMed

31.

Fang K, Xu ZJ, Jiang SX, Tang DS, Yan CS, Deng YY et al (2021) lncRNA FGD5AS1 promotes breast cancer progression by regulating the hsamiR1955p/NUAK2 axis. Mol Med Rep. https://doi.org/10.3892/mmr.2021.12099CrossRefPubMedPubMedCentral

32.

Lin J, Liao S, Liu Z, Li E, Wu X, Zeng W (2021) LncRNA FGD5-AS1 accelerates cell proliferation in pancreatic cancer by regulating miR-520a-3p/KIAA1522 axis. Cancer Biol Ther 22(3):257–266. https://doi.org/10.1080/15384047.2021.1883184CrossRefPubMedPubMedCentral

33.

Xia Y, Wang WC, Shen WH, Xu K, Hu YY, Han GH et al (2021) Thalidomide suppresses angiogenesis and immune evasion via lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis-mediated VEGFA expression and PD-1/PD-L1 checkpoint in NSCLC. Chem Biol Interact 349:109652. https://doi.org/10.1016/j.cbi.2021.109652CrossRefPubMed

34.

Zhao JB, Xue JF, Zhang WZ, Ren YL, Yan DM (2020) Long noncoding RNA FGD5-AS1 promotes glioma cell proliferation, migration and invasion by regulating wnt/beta-catenin pathway. Cancer Manag Res 12:6187–6193. https://doi.org/10.2147/CMAR.S250284CrossRefPubMedPubMedCentral

35.

Velasco MX, Kosti A, Penalva LOF, Hernandez G (2019) The diverse roles of RNA-binding proteins in glioma development. Adv Exp Med Biol 1157:29–39. https://doi.org/10.1007/978-3-030-19966-1_2CrossRefPubMed

36.

Cao H, Gao R, Yu C, Chen L, Feng Y (2019) The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4. Funct Integr Genomics 19(3):487–496. https://doi.org/10.1007/s10142-019-00661-8CrossRefPubMed

37.

Deng M, Wang N, Li Z, Chen R, Duan J, Peng Y et al (2022) FXR1 can bind with the CFIm25/CFIm68 complex and promote the progression of urothelial carcinoma of the bladder by stabilizing TRAF1 mRNA. Cell Death Dis 13(2):170. https://doi.org/10.1038/s41419-022-04614-1CrossRefPubMedPubMedCentral

38.

Li L, Jin Y, Wang X, Wang L, Sun Y, Luo Y et al (2021) Long noncoding RNA ENST00000508435 promotes migration of breast cancer via FXR 1. Cell Adhes Migr 15(1):140–151. https://doi.org/10.1080/19336918.2021.1921402CrossRef

Titel: FXR1 promotes glioma progression by downregulating microRNA-124-3p through long noncoding RNA FGD5-AS1 upregulation
verfasst von: Xin Gong
Mengyi Huang
Lei Chen
Huan Zeng
Publikationsdatum: 19.04.2023
Verlag: Springer International Publishing
Erschienen in: Acta Neurologica Belgica / Ausgabe 4/2023
Print ISSN: 0300-9009
Elektronische ISSN: 2240-2993
DOI: https://doi.org/10.1007/s13760-023-02263-5

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Viertel reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2023

Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis mimicking as cerebral amyloid angiopathy in a 78-year-old gentleman

Temporal lobe atrophy as a potential predictor of functional outcome in older adults with acute ischemic stroke

Leukoaraiosis severity is related to increased risk of early neurological deterioration in acute ischemic stroke: a retrospective observational study

Cyclic vomiting syndrome, a common language? A 20-year bibliometric study

Neuronal intranuclear inclusion disease: a case report and literature review