LncRNA‐Mediated TPI1 and PKM2 Promote Self‐Renewal and Chemoresistance in GBM

Abstract: Temozolomide (TMZ) resistance is one of the major reasons for poor prognosis in patients with glioblastoma (GBM). Long noncoding RNAs (lncRNAs) are involved in multiple biological processes, including TMZ resistance. Linc00942 is a potential regulator of TMZ sensitivity in GBM cells is shown previously. However, the underlying mechanism of TMZ resistance induced by Linc00942 is unknown. In this study, the sequence of Linc00942 by rapid amplification of cDNA ends assay in TMZ‐resistant GBM cells is identified and confirmed that Linc00942 contributes to self‐renewal and TMZ resistance in GBM cells. Chromatin isolation by RNA purification followed by mass spectrometry (ChIRP‐MS) and followed by Western blotting (ChIRP‐WB) assays shows that Linc00492 interacted with TPI1 and PKM2, subsequently promoting their phosphorylation, dimerization, and nuclear translocation. The interaction of Linc00942 with TPI1 and PKM2 leads to increased acetylation of H3K4 and activation of the STAT3/P300 axis, resulting in the marked transcriptional activation of SOX9. Moreover, the knockdown of SOX9 reversed TMZ resistance induced by Linc00492 both in vitro and in vivo. In summary, Linc00942 strongly promotes SOX9 expression by interacting with TPI1 and PKM2 is found, thereby driving self‐renewal and TMZ resistance in GBM cells. These findings suggest potential combined therapeutic strategies to overcome TMZ resistance in patients with GBM.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
LncRNA‐Mediated TPI1 and PKM2 Promote Self‐Renewal and Chemoresistance in GBM ; day:28 ; month:09 ; year:2024 ; extent:18
Advanced science ; (28.09.2024) (gesamt 18)

Urheber
Yang, Changxiao
Li, Ziwei
Tian, Kaifu
Meng, Xiangqi
Wang, Xinyu
Song, Dan
Wang, Xuan
Xu, Tianye
Sun, Penggang
Zhong, Junzhe
Song, Yu
Ma, Wenbin
Liu, Yuxiang
Yu, Daohan
Shen, Ruofei
Jiang, Chuanlu
Cai, Jinquan

DOI
10.1002/advs.202402600
URN
urn:nbn:de:101:1-2409291409219.433692395038
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:30 MESZ

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Beteiligte

  • Yang, Changxiao
  • Li, Ziwei
  • Tian, Kaifu
  • Meng, Xiangqi
  • Wang, Xinyu
  • Song, Dan
  • Wang, Xuan
  • Xu, Tianye
  • Sun, Penggang
  • Zhong, Junzhe
  • Song, Yu
  • Ma, Wenbin
  • Liu, Yuxiang
  • Yu, Daohan
  • Shen, Ruofei
  • Jiang, Chuanlu
  • Cai, Jinquan

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