Hypoxia-induced LncRNA PDIA3P1 Promotes Mesenchymal Transition Via Sponging of MiR-124-3p in Glioma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Mar 5

PMID 32127518

Citations 34

Authors

Shaobo Wang

Yanhua Qi

Xiao Gao

Wei Qiu

Qinglin Liu

Xiaofan Guo

Mingyu Qian

Zihang Chen

Zongpu Zhang

Huizhi Wang

Jianye Xu

Hao Xue

Xing Guo

Ping Zhang

Rongrong Zhao

Gang Li

Affiliations

Soon will be listed here.

Abstract

Hypoxia is a critical factor in the malignant progression of glioma, especially for the highly-invasive mesenchymal (MES) subtype. But the detailed mechanisms in hypoxia-induced glioma MES transition remain elusive. Pseudogenes, once considered to be non-functional relics of evolution, are emerging as a critical factor in human tumorigenesis and progression. Here, we investigated the clinical significance, biological function, and mechanisms of protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) in hypoxia-induced glioma MES transition. In this study, we found that PDIA3P1 expression was closely related to tumor degree, transcriptome subtype, and prognosis in glioma patients. Enrichment analysis found that high PDIA3P1 expression was associated with epithelial-mesenchymal transition, extracellular matrix (ECM) disassembly, and angiogenesis. In vitro study revealed that overexpression of PDIA3P1 enhanced the migration and invasion capacity of glioma cells, while knockdown of PDIA3P1 induced the opposite effect. Further studies revealed that PDIA3P1 functions as a ceRNA, sponging miR-124-3p to modulate RELA expression and activate the downstream NF-κB pathway, thus promoting the MES transition of glioma cells. In addition, Hypoxia Inducible Factor 1 was confirmed to directly bind to the PDIA3P1 promotor region and activate its transcription. In conclusion, PDIA3P1 is a crucial link between hypoxia and glioma MES transition through the PDIA3P1-miR-124-3p-RELA axis, which may serve as a prognostic indicator and potential therapeutic target for glioma treatment.

Citing Articles

Cell-Based Glioma Models for Anticancer Drug Screening: From Conventional Adherent Cell Cultures to Tumor-Specific Three-Dimensional Constructs.

Lanskikh D, Kuziakova O, Baklanov I, Penkova A, Doroshenko V, Buriak I Cells. 2025; 13(24.

PMID: 39768176 PMC: 11674823. DOI: 10.3390/cells13242085.

Methionine deprivation inhibits glioma proliferation and EMT via the TP53TG1/miR-96-5p/STK17B ceRNA pathway.

Li J, Liu R, Hu H, Huang Y, Shi Y, Li H NPJ Precis Oncol. 2024; 8(1):270.

PMID: 39572759 PMC: 11582638. DOI: 10.1038/s41698-024-00763-y.

Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma.

Fu Z, Chen Z, Ye J, Ji J, Ni W, Lin W Cancers (Basel). 2024; 16(4).

PMID: 38398231 PMC: 10887327. DOI: 10.3390/cancers16040840.

Copy number gain of FAM131B-AS2 promotes the progression of glioblastoma by mitigating replication stress.

Wang S, Qi Y, Zhao R, Pan Z, Li B, Qiu W Neuro Oncol. 2024; 26(6):1027-1041.

PMID: 38285005 PMC: 11145449. DOI: 10.1093/neuonc/noae014.

UBDP1 pseudogene and UBD network competitively bind miR‑6072 to promote glioma progression.

Hong F, Gong Z, Chen C, Hua T, Huang Q, Liu Y Int J Oncol. 2024; 64(3).

PMID: 38275102 PMC: 10836499. DOI: 10.3892/ijo.2024.5617.

References

LaPointe S, Perry A, Butowski N . Primary brain tumours in adults. Lancet. 2018; 392(10145):432-446. DOI: 10.1016/S0140-6736(18)30990-5. View

Lim M, Xia Y, Bettegowda C, Weller M . Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018; 15(7):422-442. DOI: 10.1038/s41571-018-0003-5. View

Zhao J, Chen A, Gartrell R, Silverman A, Aparicio L, Chu T . Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat Med. 2019; 25(3):462-469. PMC: 6810613. DOI: 10.1038/s41591-019-0349-y. View

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1):98-110. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

Jin X, Kim L, Wu Q, Wallace L, Prager B, Sanvoranart T . Targeting glioma stem cells through combined BMI1 and EZH2 inhibition. Nat Med. 2017; 23(11):1352-1361. PMC: 5679732. DOI: 10.1038/nm.4415. View

Molinaro A, Taylor J, Wiencke J, Wrensch M . Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol. 2019; 15(7):405-417. PMC: 7286557. DOI: 10.1038/s41582-019-0220-2. View

Uszczynska-Ratajczak B, Lagarde J, Frankish A, Guigo R, Johnson R . Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Genet. 2018; 19(9):535-548. PMC: 6451964. DOI: 10.1038/s41576-018-0017-y. View

Jandura A, Krause H . The New RNA World: Growing Evidence for Long Noncoding RNA Functionality. Trends Genet. 2017; 33(10):665-676. DOI: 10.1016/j.tig.2017.08.002. View

Flynn R, Chang H . Long noncoding RNAs in cell-fate programming and reprogramming. Cell Stem Cell. 2014; 14(6):752-61. PMC: 4120821. DOI: 10.1016/j.stem.2014.05.014. View

10.

Gao X, Guo X, Xue H, Qiu W, Guo X, Zhang J . lncTCF7 is a negative prognostic factor, and knockdown of lncTCF7 inhibits migration, proliferation and tumorigenicity in glioma. Sci Rep. 2017; 7(1):17456. PMC: 5727168. DOI: 10.1038/s41598-017-17340-y. View

11.

Lee J . Epigenetic regulation by long noncoding RNAs. Science. 2012; 338(6113):1435-9. DOI: 10.1126/science.1231776. View

12.

Birnbaum M, CREE E, Rasmussen H, Lewis P, CURTIS J . Effects of intermittent positive pressure breathing on emphysematous patients. Am J Med. 1966; 41(4):552-61. DOI: 10.1016/0002-9343(66)90217-8. View

13.

Karreth F, Reschke M, Ruocco A, Ng C, Chapuy B, Leopold V . The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell. 2015; 161(2):319-32. PMC: 6922011. DOI: 10.1016/j.cell.2015.02.043. View

14.

Gooding G . Small hyperechoic nodules of the renal parenchyma. J Clin Ultrasound. 1986; 14(4):322. DOI: 10.1002/jcu.1870140419. View

15.

PACE T, Ponzi M, Dore E, Scotti R, Mons B . Presence of contaminating mitochondrial DNA from host reticulocytes in experimental infections of Plasmodium berghei. Mol Biochem Parasitol. 1989; 37(1):109-13. DOI: 10.1016/0166-6851(89)90107-2. View

16.

Lu K, Chang J, Parachoniak C, Pandika M, Aghi M, Meyronet D . VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex. Cancer Cell. 2012; 22(1):21-35. PMC: 4068350. DOI: 10.1016/j.ccr.2012.05.037. View

17.

Piao Y, Liang J, Holmes L, Zurita A, Henry V, Heymach J . Glioblastoma resistance to anti-VEGF therapy is associated with myeloid cell infiltration, stem cell accumulation, and a mesenchymal phenotype. Neuro Oncol. 2012; 14(11):1379-92. PMC: 3480262. DOI: 10.1093/neuonc/nos158. View

18.

Colwell N, Larion M, Giles A, Seldomridge A, Sizdahkhani S, Gilbert M . Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells. Neuro Oncol. 2017; 19(7):887-896. PMC: 5570138. DOI: 10.1093/neuonc/now258. View

19.

Kong Y, Zhang L, Huang Y, He T, Zhang L, Zhao X . Pseudogene PDIA3P1 promotes cell proliferation, migration and invasion, and suppresses apoptosis in hepatocellular carcinoma by regulating the p53 pathway. Cancer Lett. 2017; 407:76-83. DOI: 10.1016/j.canlet.2017.07.031. View

20.

Sun C, Zhang L, Li G, Li S, Chen Z, Fu Y . The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2. Mol Ther Nucleic Acids. 2017; 9:100-110. PMC: 5626923. DOI: 10.1016/j.omtn.2017.08.015. View