Targeting HOTAIRM1 Ameliorates Glioblastoma by Disrupting Mitochondrial Oxidative Phosphorylation and Serine Metabolism

Overview

Journal iScience

Publisher Cell Press

Date 2022 Aug 22

PMID 35992092

Authors

Wei Han

Shanshan Wang

Yingjiao Qi

Fan Wu

Ningyu Tian

Boqin Qiang

Xiaozhong Peng

Affiliations

Soon will be listed here.

Abstract

Serine hydroxymethyltransferase 2 (SHMT2), which catalyzes the conversion of serine to glycine and one-carbon transfer reactions in mitochondria, is significantly upregulated in glioblastoma (GBM). However, the mechanism by which the stability of gene expression is maintained to drive GBM tumorigenesis has not been clarified. Herein, through microarray screening, we identified that HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) modulates the SHMT2 level in various GBM cell lines. Serine catabolism and mitochondrial oxidative phosphorylation activities were decreased by HOTAIRM1 inhibition. Mechanistically, according to our mass spectrometry and eCLIP-seq results, HOTAIRM1 can bind to PTBP1 and IGF2BP2. Furthermore, HOTAIRM1 maintains the stability of by promoting the recognition of an mA site and the interaction of PTBP1/IGF2BP2 with mRNA. The stability of HOTAIRM1 can also be enhanced and results in positive feedback regulation to support the progression of GBM. Thus, targeting HOTAIRM1 could be a promising metabolic therapy for GBM.

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References

LaGory E, Wu C, Taniguchi C, Ding C, Chi J, von Eyben R . Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma. Cell Rep. 2015; 12(1):116-127. PMC: 4518559. DOI: 10.1016/j.celrep.2015.06.006. View

Xie Q, Wu Q, Horbinski C, Flavahan W, Yang K, Zhou W . Mitochondrial control by DRP1 in brain tumor initiating cells. Nat Neurosci. 2015; 18(4):501-10. PMC: 4376639. DOI: 10.1038/nn.3960. View

Wang R, Li J, Bao B, Wu H, Du Z, Su J . MicroRNA-873 (miRNA-873) inhibits glioblastoma tumorigenesis and metastasis by suppressing the expression of IGF2BP1. J Biol Chem. 2015; 290(14):8938-48. PMC: 4423684. DOI: 10.1074/jbc.M114.624700. View

Chen Y, Wu J, Lin X, Bao Y, Chen Z, Zhang C . Differential lncRNA expression profiles in recurrent gliomas compared with primary gliomas identified by microarray analysis. Int J Clin Exp Med. 2015; 8(4):5033-43. PMC: 4483865. View

Banh R, Biancur D, Yamamoto K, Sohn A, Walters B, Kuljanin M . Neurons Release Serine to Support mRNA Translation in Pancreatic Cancer. Cell. 2020; 183(5):1202-1218.e25. PMC: 8100789. DOI: 10.1016/j.cell.2020.10.016. View

Van Nostrand E, Freese P, Pratt G, Wang X, Wei X, Xiao R . A large-scale binding and functional map of human RNA-binding proteins. Nature. 2020; 583(7818):711-719. PMC: 7410833. DOI: 10.1038/s41586-020-2077-3. View

Yang X, Wang Z, Li X, Liu B, Liu M, Liu L . SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation. Cancer Res. 2017; 78(2):372-386. DOI: 10.1158/0008-5472.CAN-17-1912. View

Liang Q, Li X, Guan G, Xu X, Chen C, Cheng P . Long non-coding RNA, HOTAIRM1, promotes glioma malignancy by forming a ceRNA network. Aging (Albany NY). 2019; 11(17):6805-6838. PMC: 6756894. DOI: 10.18632/aging.102205. View

Briata P, Gherzi R . Long Non-Coding RNA-Ribonucleoprotein Networks in the Post-Transcriptional Control of Gene Expression. Noncoding RNA. 2020; 6(3). PMC: 7549350. DOI: 10.3390/ncrna6030040. View

10.

Jiang T, Nam D, Ram Z, Poon W, Wang J, Boldbaatar D . Clinical practice guidelines for the management of adult diffuse gliomas. Cancer Lett. 2020; 499:60-72. DOI: 10.1016/j.canlet.2020.10.050. View

11.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

12.

Rea J, Menci V, Tollis P, Santini T, Armaos A, Garone M . HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade. Cell Death Dis. 2020; 11(7):527. PMC: 7359305. DOI: 10.1038/s41419-020-02738-w. View

13.

Lucas S, Chen G, Aras S, Wang J . Serine catabolism is essential to maintain mitochondrial respiration in mammalian cells. Life Sci Alliance. 2018; 1(2):e201800036. PMC: 6238390. DOI: 10.26508/lsa.201800036. View

14.

Tan A, Ashley D, Lopez G, Malinzak M, Friedman H, Khasraw M . Management of glioblastoma: State of the art and future directions. CA Cancer J Clin. 2020; 70(4):299-312. DOI: 10.3322/caac.21613. View

15.

Marrocco I, Altieri F, Rubini E, Paglia G, Chichiarelli S, Giamogante F . Shmt2: A Stat3 Signaling New Player in Prostate Cancer Energy Metabolism. Cells. 2019; 8(9). PMC: 6770108. DOI: 10.3390/cells8091048. View

16.

Van Nostrand E, Pratt G, Shishkin A, Gelboin-Burkhart C, Fang M, Sundararaman B . Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat Methods. 2016; 13(6):508-14. PMC: 4887338. DOI: 10.1038/nmeth.3810. View

17.

Wei S, Zhao M, Wang X, Li Y, Wang K . PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation. J Hematol Oncol. 2016; 9(1):44. PMC: 4857283. DOI: 10.1186/s13045-016-0274-1. View

18.

Nikiforov M, Chandriani S, OConnell B, Petrenko O, Kotenko I, Beavis A . A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism. Mol Cell Biol. 2002; 22(16):5793-800. PMC: 133987. DOI: 10.1128/MCB.22.16.5793-5800.2002. View

19.

Cheng G, Zhang Q, Pan J, Lee Y, Ouari O, Hardy M . Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis. Nat Commun. 2019; 10(1):2205. PMC: 6525201. DOI: 10.1038/s41467-019-10042-1. View

20.

Zhang X, Weissman S, Newburger P . Long intergenic non-coding RNA HOTAIRM1 regulates cell cycle progression during myeloid maturation in NB4 human promyelocytic leukemia cells. RNA Biol. 2014; 11(6):777-87. PMC: 4156508. DOI: 10.4161/rna.28828. View