Abstract
Objective
The study is to research how miR-34-SIRT1 is regulated during hypoxia in lung cancer cells.
Results
Analysis of publicly available datasets from patients with NSCLC did not reveal significant genomic alterations in RBM38, SIRT1, HIF1A, MIR34A, MIR34B, and MIR34C, but expectedly revealed alterations in TP53. Overall survival in NSCLC patients with or without alterations in these genes was not significantly different. When expanded to include all lung cancer patients, overall survival was significantly lower in patients with genomic alterations in these genes.
Conclusions
Cumulatively, our results reveal a novel mechanism of RBM38-mediated regulation of the HIF1A/miR-34a/SIRT1/p53 axis under hypoxia in NSCLC cells.
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References
Ahn YH, Gibbons DL, Chakravarti D et al (2012) ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression. J Clin Invest 122:3170–3183. https://doi.org/10.1172/JCI63608
Amelio I, Melino G (2015) The p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression. Trends Biochem Sci 40:425–434. https://doi.org/10.1016/j.tibs.2015.04.007
Bommer GT, Gerin I, Feng Y et al (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17:1298–1307. https://doi.org/10.1016/j.cub.2007.06.068
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492
Campbell JD, Alexandrov A, Kim J et al (2016) Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet 48:607–616. https://doi.org/10.1038/ng.3564
Chang TC, Wentzel EA, Kent OA et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745–752. https://doi.org/10.1016/j.molcel.2007.05.010
Cho SJ, Teng IF, Zhang M, Yin T, Jung YS, Zhang J, Chen X (2015) Hypoxia-inducible factor 1 alpha is regulated by RBM38, a RNA-binding protein and a p53 family target, via mRNA translation. Oncotarget 6:305–316. https://doi.org/10.18632/oncotarget.2786
Christoffersen NR, Shalgi R, Frankel LB, Leucci E, Lees M, Klausen M, Pilpel Y, Nielsen FC, Oren M, Lund AH (2010) p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ 17:236–245. https://doi.org/10.1038/cdd.2009.109
Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY (2007) MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res 67:8433–8438. https://doi.org/10.1158/0008-5472.CAN-07-1585
Del Vescovo V, Denti MA (2015) microRNA and lung cancer. Adv Exp Med Biol 889:153–177. https://doi.org/10.1007/978-3-319-23730-5_9
Gao J, Aksoy BA, Dogrusoz U et al (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6:l1. https://doi.org/10.1126/scisignal.2004088
He L, He X, Lim LP et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134. https://doi.org/10.1038/nature05939
Heinicke LA, Nabet B, Shen S, Jiang P, van Zalen S, Cieply B, Russell JE, Xing Y, Carstens RP (2013) The RNA binding protein RBM38 (RNPC1) regulates splicing during late erythroid differentiation. PloS ONE 8:e78031. https://doi.org/10.1371/journal.pone.0078031
Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359:1367–1380
Jamal-Hanjani M, Wilson GA, McGranahan N et al (2017) Tracking the evolution of non-small-cell lung cancer. N Engl J Med 376:2109–2121. https://doi.org/10.1056/NEJMoa1616288
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647. https://doi.org/10.1016/j.cell.2005.01.014
Jordan EJ, Kim HR, Arcila ME et al (2017) Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov 7:5 96–609. https://doi.org/10.1158/2159-8290.CD-16-1337
Kim JS, Kim EJ, Lee S et al (2019) MiR-34a and miR-34b/c have distinct effects on the suppression of lung adenocarcinomas. Exp Mol Med 51:9. https://doi.org/10.1038/s12276-018-0203-1
Li G, Fang J, Wang Y, Wang H, Sun CC (2018) MiRNA-based therapeutic strategy in lung cancer. Curr Pharm Des 23:6011–6018. https://doi.org/10.2174/1381612823666170725141954
Lucchesi CA, Zhang J, Ma B, Chen M, Chen X (2019) Disruption of the Rbm38-eIF4E complex with a synthetic peptide Pep8 increases p53 expression. Cancer Res 79:807–818. https://doi.org/10.1158/0008-5472.CAN-18-2209
Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D (2011) RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 11:761–774. https://doi.org/10.1038/nrc3106
Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26:731–743. https://doi.org/10.1016/j.molcel.2007.05.017
Rizvi H, Sanchez-Vega F, La K et al (2018) Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol 36:633–641. https://doi.org/10.1200/JCO.2017.75.3384
Rizvi NA, Hellmann MD, Snyder A et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. https://doi.org/10.1126/science.aaa1348
Shu L, Yan W, Chen X (2006) RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. Genes Dev 20:2961–2972. https://doi.org/10.1101/gad.1463306
Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, Meister G, Hermeking H (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6:1586–1593. https://doi.org/10.4161/cc.6.13.4436
U.S. Cancer Statistics Working Group. Atlanta (GA) (2010) U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute
Unberath P, Knell C, Prokosch HU, Christoph J (2019) Developing new analysis functions for a translational research platform: extending the cBioPortal for cancer genomics. Stud Health Technol Inform 258:46–50
Vavalà T, Monica V, Lo Iacono M, Mele T, Busso S, Righi L, Papotti M, Scagliotti GV, Novello S (2017) Precision medicine in age-specific non-small-cell-lung-cancer patients: integrating biomolecular results into clinical practice: a new approach to improve personalized translational research. Lung Cancer 107:84–90. https://doi.org/10.1016/j.lungcan.2016.05.021
Warzecha CC, Sato TK, Nabet B, Hogenesch JB, Carstens RP (2009) ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing. Mol cell 33:591–601. https://doi.org/10.1016/j.molcel.2009.01.025
Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 105:13421–13426. https://doi.org/10.1073/pnas.0801613105
Zhang J, Cho SJ, Shu L, Yan W, Guerrero T, Kent M, Skorupski K, Chen H, Chen X (2011) Translational repression of p53 by RNPC1, a p53 target overexpressed in lymphomas. Genes Dev 25:1528–1543. https://doi.org/10.1101/gad.2069311
Zhang J, Xu E, Ren C, Yan W, Zhang M, Chen M, Cardiff RD, Imai DM, Wisner E, Chen X (2014) Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors. Proc Natl Acad Sci USA 111:18637–18642. https://doi.org/10.1073/pnas.1415607112
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This study was supported by Heilongjiang Province Applied Technology Research and Development Program (GZ19C01).
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Lin, Qy., Yin, Hl. RBM38 induces SIRT1 expression during hypoxia in non-small cell lung cancer cells by suppressing MIR34A expression. Biotechnol Lett 42, 35–44 (2020). https://doi.org/10.1007/s10529-019-02766-3
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DOI: https://doi.org/10.1007/s10529-019-02766-3