LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

Haijuan Fu; Zhaoyu Zhang; Danyang Li; Qingqing Lv; Simin Chen; Zuping Zhang; Minghua Wu

doi:10.3389/fonc.2022.817737

LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

Front Oncol. 2022 Apr 28:12:817737. doi: 10.3389/fonc.2022.817737. eCollection 2022.

Authors

Haijuan Fu^{1

2}, Zhaoyu Zhang^{1

2}, Danyang Li^{1

2}, Qingqing Lv^{1

2}, Simin Chen³, Zuping Zhang⁴, Minghua Wu^{1

2}

Affiliations

¹ Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
² The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, China.
³ Department of Clinical Laboratory, Yueyang Central Hospital, Yueyang, China.
⁴ Department of Pathogeny Biology, School of Basic Medical Science, Central South University, Changsha, China.

Abstract

PELATON is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (LINC01272). The known reports showed that PELATON functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that PELATON, as an onco-lncRNA, alleviates the ferroptosis driven by mutant p53 and promotes mutant p53-mediated GBM proliferation. We also first confirmed that PELATON is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant P53 mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of SLC7A11, and inhibits the expression of ACSL4 and COX2.PELATON can inhibit the expression of p53 in p53 wild-type GBM cells and regulate the expression of BACH1 and CD44, but it has no effect on p53, BACH1 and CD44 in p53 mutant GBM cells. PELATON and p53 can form a complex through the RNA binding protein EIF4A3. Knockdown of PELATON resulted in smaller mitochondria, increased mitochondrial membrane density, and enhanced sensitivity to ferroptosis inducers to inhibit GBM cell proliferation and invasion. In addition, we established a favourite prognostic model with NCOA4 and PELATON. PELATON is a promising target for the prognosis and treatment of GBM.

Keywords: LINC01272; PELATON; ROS; ferroptosis; lncRNA.