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LINC00174 down-regulation decreases chemoresistance to temozolomide in human glioma cells by regulating miR-138-5p/SOX9 axis

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Abstract

Temozolomide (TMZ) is one of the most common drugs selected for glioma chemotherapy, but the therapeutic effect of glioma treatment is usually limited due to its resistance. Long non-coding RNA (lncRNA) is gradually found to be a vital regulator in numerous physiological and pathological processes. Lately, it was revealed that LINC00174 could promote CRC cell growth. However, the function and potential regulatory manner of LINC00174 in glioma remain unclear. Our results demonstrated that the expression level of LINC00174 was higher in glioma tissues, and LINC00174 down-regulation could remarkably prevent cell proliferation and promote cell apoptosis in both glioma cells and TMZ-resistant glioma cells. Mechanistic studies revealed that LINC00174 can sponge microRNA-138-5p (miR-138-5p) and down-regulate its expression, thereby up-regulating the protein level of miR-138-5p’s target, sex-determining region Y (SRY)-box9 protein (SOX9). Additionally, in vivo experiments revealed that LINC00174 shRNA can serve as a tumor suppressor through down-regulating SOX9 in glioma. In this study, a novel established regulatory way of LINC00174/miR-138-5p/SOX9 axis was systematically studied, which may provide a new manner for glioma therapy.

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Funding

This work was supported by The fund of Shaanxi Key Laboratory of Brain Disorders (Grant No. 18NBZD01).

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Authors and Affiliations

  1. Department of Emergency Critical Care Unit, Sanya People’s Hospital, Sanya, Hainan, 572000, China

    Bin Li

  2. Department of Neurosurgery, Second Affiliated Hospital of Xi’an Medical University, No. 167, Fangdong Street, Baqiao District, Xi’an, Shaanxi, 710038, China

    Haikang Zhao, Fenglu Wang & Mingsheng Chen

  3. Department of Nursing, Sanya People’s Hospital, Sanya, Hainan, 572000, China

    Jianming Song

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  1. Bin Li
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Contributions

MSC conceived and designed the experiments, FLW and JMS analyzed and interpreted the results of the experiments, HKZ and BL performed the experiments.

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Correspondence to Mingsheng Chen.

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13577_2019_281_MOESM1_ESM.jpg

Figure S1 (A) Relative MGMT methylation status in the established TMZ-resistant sublines of U251 and U87, and in parent U251 and U87 cell lines, as determined using methylation-specific polymerase chain reaction. (B) Relative proliferation of LN229 cells after transfected with sh-LINC00174 or sh-NC and treated with different doses of TMZ were, respectively, determined by CCK-8. TMZ treatment significantly decreased cell proliferation in a dose-dependent manner. IC50 was calculated using the sigmoidal dose–response function of GraphPad Prism. (C) Kaplan–Meier curves of overall survival of 30 glioblastoma patients, stratified by LINC00174 expression. The data are expressed as the mean ± SEM, **P < 0.01 (JPEG 744 kb)

13577_2019_281_MOESM2_ESM.jpg

Figure S2 The relative miR-1910-3p levels in glioma tissues (tumor, n = 40) and control tissues (normal, n = 40), as determined using qRT-PCR. The data are expressed as the mean ± SEM, **P < 0.01 (JPEG 462 kb)

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Li, B., Zhao, H., Song, J. et al. LINC00174 down-regulation decreases chemoresistance to temozolomide in human glioma cells by regulating miR-138-5p/SOX9 axis. Human Cell 33, 159–174 (2020). https://doi.org/10.1007/s13577-019-00281-1

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