OncoTargets and Therapy (Feb 2021)

LINC00466 Impacts Cell Proliferation, Metastasis and Sensitivity to Temozolomide of Glioma by Sponging miR-137 to Regulate PPP1R14B Expression

  • Zhao M,
  • Shao Y,
  • Xu J,
  • Zhang B,
  • Li C,
  • Gong J

Journal volume & issue
Vol. Volume 14
pp. 1147 – 1159

Abstract

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Mingfei Zhao,1,* Yijie Shao,1,* Jinfang Xu,1 Buyi Zhang,2 Chenguang Li,1 Jie Gong3 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurointerventional, Zhejiang Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Gong Tel +86-15168248628Fax +86571-88098123Email [email protected]: LINC00466 is a newfound long non-coding RNA (lncRNA) that has been rarely explored in cancers. However, the specific role and molecular mechanism of LINC00466 in glioma remain to be further elucidated.Methods: Bioinformatic analysis was used to screen differentially expressed genes. Quantitative real-time PCR (qRT-PCR) was used to determine the expression of LINC00466, microRNA-137 (miR-137) and protein phosphatase 1 regulatory subunit 14B (PPP1R14B). Dual-luciferase reporter gene assay and RNA binding protein Immunoprecipitation (RIP) assays were employed to verify the binding relationship among LINC00466, miR-137 and PPP1R14B. The sensitivity of glioma cells to temozolomide (TMZ) was measured by cell counting kit-8 (CCK8) assay. The xenograft nude models were used to test the effects of LINC00466 on glioma tumor growth in vivo.Results: Highly expressed LINC00466 and PPP1R14B and lowly expressed miR-137 were eventually revealed in glioma tissues. Overexpression of LINC00466 could promote proliferation, metastasis and drug sensitivity to TMZ of glioma cells. LINC00466 could bind to miR-137, and up-regulation of miR-137 could attenuate the enhancing effects caused by LINC00466 overexpression. We took a further step and found that miR-137 could bind to PPP1R14B. Besides, LINC00466 could function as a sponge to miR-137 to regulate PPP1R14B. In addition, overexpression of LINC00466 could promote tumor growth in vivo.Conclusion: These findings validate LINC00466 could restrain the miR-137 expression to up-regulate PPP1R14B and therefore promote proliferation, metastasis and resistance to TMZ of glioma.Keywords: LINC00466/miR-137/PPP1R14B, glioma, proliferation and metastasis, temozolomide; TMZ

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