Long non‑coding RNA GASL1 may inhibit the proliferation of glioma cells by inactivating the TGF‑β signaling pathway

  • Authors:
    • Yuhua Hu
    • Baohua Jiao
    • Lingyou Chen
    • Man Wang
    • Xinwang Han
  • View Affiliations

  • Published online on: April 18, 2019     https://doi.org/10.3892/ol.2019.10273
  • Pages: 5754-5760
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Abstract

Growth‑arrest‑associated long non‑coding RNA (lncRNA) 1 (GASL1) is an lncRNA with a tumor suppression role in osteosarcoma, whereas its involvement in other malignancies is unknown. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with glioma, and blood samples were collected from patients and healthy controls to detect the expression of GASL1. All patients were followed up for 5 years, and the diagnostic and prognostic values for glioma were evaluated by receiver operating characteristic curve analysis and survival curve analysis, respectively. Potential associations between serum GASL1 and clinicopathological data of patients with glioma were investigated using χ2 testing. A GASL1 expression vector and short hairpin RNA targeting GASL1 were transfected into glioma cells and the effects on TGF‑β1 expression and cell proliferation were investigated by western blotting and Cell Counting Kit‑8 assay. Glioma tumor tissue exhibited significantly lower GASL1 expression compared with in adjacent healthy tissue. Serum levels of GASL1 were lower in patients compared with in healthy controls. Serum GASL1 was identified to be a sensitive biomarker for glioma cancer, and a low expression level of GASL1 was associated with a decreased postoperative survival rate. In glioma cell lines with GASL1 overexpression, TGF‑β1 expression was decreased and proliferation was inhibited. GASL1 knockdown in glioma cell lines led to increased TGF‑β1 expression and proliferation. TGF‑β1 treatment had no effect on GASL1 expression, but TGF‑β1 treatment partially rescued the inhibition of proliferation in cells overexpressing GASL1. Therefore, GASL1 may inhibit tumor growth of glioma by inactivating the TGF‑β signaling pathway.

References

1 

Goodenberger ML and Jenkins RB: Genetics of adult glioma. Cancer Genet Cytogenet. 205:613–621. 2012. View Article : Google Scholar

2 

Omuro A and DeAngelis LM: Glioblastoma and other malignant gliomas: A clinical review. JAMA. 310:1842–1850. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Mishra MV, Andrews DW, Glass J, Evans JJ, Dicker AP, Shen X and Lawrence YR: Characterization and outcomes of optic nerve gliomas: A population-based analysis. J Neurooncol. 107:591–597. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Stark AM, van de Bergh J, Hedderich J, Mehdorn HM and Nabavi A: Glioblastoma: Clinical characteristics, prognostic factors and survival in 492 patients. Clin Neurol Neurosurg. 114:840–845. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Ichimura K: Molecular pathogenesis of IDH mutations in gliomas. Brain Tumor Pathol. 29:131–139. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Radner H, El-Shabrawi Y, Eibl RH, Brüstle O, Kenner L, Kleihues P and Wiestler OD: Tumor induction by ras and myc oncogenes in fetal and neonatal brain: Modulating effects of developmental stage and retroviral dose. Acta Neuropathol. 86:456–465. 1993. View Article : Google Scholar : PubMed/NCBI

7 

Kaminska B, Kocyk M and Kijewska M: TGF-beta signaling and its role in glioma pathogenesis. Adv Exp Med Biol. 986:171–187. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Bruna A, Darken RS, Rojo F, Ocaña A, Peñuelas S, Arias A, Paris R, Tortosa A, Mora J, Baselga J and Seoane J: High TGF-beta Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 11:147–160. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Akhurst RJ and Derynck R: TGF-beta signaling in cancer-a double-edged sword. Trends Cell Biol. 11:S44–S51. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Yang G, Lu X and Yuan L: LncRNA: A link between RNA and cancer. Biochim Biophys Acta. 1839:1097–1109. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Kiang KM, Zhang XQ and Leung GK: Long non-coding RNAs: The key players in glioma pathogenesis. Cancers (Basel). 7:1406–1424. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Yuan JH, Yang F, Wang F, Ma JZ, Guo YJ, Tao QF, Liu F, Pan W, Wang TT, Zhou CC, et al: A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell. 25:666–681. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Gasri-Plotnitsky L, Ovadia A, Shamalov K, Nizri-Megnaji T, Meir S, Zurer I, Cohen CJ and Ginsberg D: A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity. Oncotarget. 8:23775–23786. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Yao J, Zhou B, Zhang J, Geng P, Liu K, Zhu Y and Zhu W: A new tumor suppressor LncRNA ADAMTS9-AS2 is regulated by DNMT1 and inhibits migration of glioma cells. Tumour Biol. 35:7935–7944. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, Qian J, Liu N and You Y: Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 9:e862952014. View Article : Google Scholar : PubMed/NCBI

17 

Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF and Tewari M: Blood cell origin of circulating microRNAs: A cautionary note for cancer biomarker studies. Cancer Prev Res (Phila). 5:492–497. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Lei B, Xiang W, Yu M, Yu L and Qi S: Case report glioma progress and extracranial systemic multiple metastasis: A case report. Int J Clin Exp Med. 9:16883–16886. 2016.

19 

Derynck R, Akhurst RJ and Balmain A: TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 29:117–129. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Bellam N and Pasche B: TGF-β signaling alterations and colon cancer. Cancer Treat Res. 155:85–103. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Li Z, Dong M, Fan D, Hou P, Li H, Liu L, Lin C, Liu J, Su L, Wu L, et al: LncRNA ANCR down-regulation promotes TGF-β-induced EMT and metastasis in breast cancer. Oncotarget. 8:67329–67343. 2017.PubMed/NCBI

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June 2019
Volume 17 Issue 6

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Copy and paste a formatted citation
APA
Hu, Y., Jiao, B., Chen, L., Wang, M., & Han, X. (2019). Long non‑coding RNA GASL1 may inhibit the proliferation of glioma cells by inactivating the TGF‑β signaling pathway. Oncology Letters, 17, 5754-5760. https://doi.org/10.3892/ol.2019.10273
MLA
Hu, Y., Jiao, B., Chen, L., Wang, M., Han, X."Long non‑coding RNA GASL1 may inhibit the proliferation of glioma cells by inactivating the TGF‑β signaling pathway". Oncology Letters 17.6 (2019): 5754-5760.
Chicago
Hu, Y., Jiao, B., Chen, L., Wang, M., Han, X."Long non‑coding RNA GASL1 may inhibit the proliferation of glioma cells by inactivating the TGF‑β signaling pathway". Oncology Letters 17, no. 6 (2019): 5754-5760. https://doi.org/10.3892/ol.2019.10273