Skip to main content
SpringerLink
Log in

How long noncoding RNAs enforce their will on mitochondrial activity: regulation of mitochondrial respiration, reactive oxygen species production, apoptosis, and metabolic reprogramming in cancer

Current Genetics Aims and scope Submit manuscript

Abstract

The cellular transcriptome contains a wide diversity of untranslated RNAs, of which the class of regulatory long noncoding RNAs (lncRNAs) has only recently been recognized. Evidence swiftly accumulates of lncRNAs influencing mitochondrial activities of eukaryotic cells, and perturbed expression is conspicuously associated with human diseases. In this review, we describe the multifaceted effects of lncRNAs on mitochondrial function, more particularly on the balance between oxidative phosphorylation and glycolysis, on the production of reactive oxygen species, and on apoptosis in human cells. Emphasis is placed on the involvement of lncRNAs in cancer metabolism, as tumor cells rely heavily on modifications of mitochondrial functioning as an essential component for sustained tumorigenesis and cancer progression. From the nonexhaustive list of lncRNAS described in this review, ANRIL, AScmtRNA, H19, HOTAIR, LincRNA-p21, MALAT1, RMRP, SAMMSON, and VL30 have emerged as potent regulators of mitochondrial metabolism. Due to their key role in cancer progression, they represent potential targets of innovative lncRNA-based treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Aloni Y, Attardi G (1971) Symmetrical in vivo transcription of mitochondrial DNA in HeLa cells. Proc Natl Acad Sci USA 68:1757–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altieri DC (2010) Survivin and IAP proteins in cell-death mechanisms. Biochem J 30:199–205

    Article  Google Scholar 

  • Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    Article  CAS  PubMed  Google Scholar 

  • Antonika H, Sasarman F, Nishimura T, Paupe V, Shoubridge EA (2013) The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression. Cell Metab 17:386–398

    Article  Google Scholar 

  • Ardekani AM, Moslemi Naeini M (2010) The role of MicroRNAs in human diseases. Avicenna J Med Biotech 2:161–179

    CAS  Google Scholar 

  • Arun G, Diermeier S, Akerman M, Chang KC, Wilkinson E, Hearn S, Kim Y, MacLeod R, Krainer AR, Norton L, Brogi E, Egeblad M, Spector DL (2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 30:34–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barakat TS, Gribnau J (2012) X chromosome inactivation in the cycle of life. Development 139:2085–2089

    Article  CAS  PubMed  Google Scholar 

  • Bianchesi V, Badi I, Bertolotti M, Nigro P, D’Allessandra Y, Capogrossi MC, Zanobini M, Pompilio G, Raucci A, Lauri A (2015) The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in endothelial cells. J Mol Cell Cardiol 81:62–70

    Article  Google Scholar 

  • Borgna V, Villegas J, Burzio VA, Belmar S, Araya M, Jeldes E, Lobos-Gonzalez L, Silva V, Villota C, Oliveira-Cruz L, Lopez C, Socias T, Castillo O, Burzio LO (2017) Mitochodnrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model. Oncotarget 8:43692–43708

    Article  PubMed  PubMed Central  Google Scholar 

  • Burzio VA, Villota C, Villegas J, Landerer E, Boccardo E, Villa LL, Martinez R, Lopez C, Gaete F, Toro V, Rodriguez X, Burzio LO (2009) Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells. Proc Natl Acad Sci 106:9430–9434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cannino G, Di Liegro CM, Rinaldi AM (2007) Nuclear-mitochondrial interaction. Mitochondrion 7:359–366

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Liang H, Yang H, Zhou K, Xu L, Liu J, Lai B, Song L, Luo H, Peng J, Liu Z, Xiao Y, Chen W, Tang H (2017) LincRNa-p21: function and mechanism in cancer. Med Oncol 34:e98

    Article  Google Scholar 

  • Chiou SK, Jones MK, Tarnawski AS (2003) Survivin—an anti-apoptosis protein: its biological roles and implications for cancer and beyond. Med Sci Monit 9:125–129

    Google Scholar 

  • Christianson TW, Clayton DA (1988) A tridecamer DNA sequence supports human mitochondrial RNA 3′-end formation in vitro. Mol Cell Biol 8:4502–4509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656

    Article  CAS  PubMed  Google Scholar 

  • Das J, Podder S, Ghosh TC (2014) Insights into the miRNA regulations in human disease genes. BMC Genom 15:e1010

    Article  Google Scholar 

  • Davies KJ (2000) Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life 50:279–289

    Article  CAS  PubMed  Google Scholar 

  • De Paepe B (2012) Mitochondrial markers for cancer: relevance to diagnosis, therapy, and prognosis and general understanding of malignant disease mechanisms. ISRN Pathol. doi:10.5402/2012/217162

    Google Scholar 

  • Du Z, Fei T, Verhaak RG, Su Z, Zhang Y, Brown M, Chen Y, Liu XS (2013) Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol 20:908–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, Rustin P, Gustafsson CM, Larsson NG (2004) Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 13:935–944

    Article  CAS  PubMed  Google Scholar 

  • Fogal V, Richardson AD, Karmali PP, Scheffler IE, Smith JW, Ruoslathi E (2010) Mitochondrial p32 protein is a critical regulator of tumor metabolism via maintenance of oxidative phosphorylation. Mol Cell Biol 30:1303–1318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulco M, Sartorelli V (2008) Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell Cycle 7:3669–3679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galluzzi L, Kroemer G (2007) Mitochondrial apoptosis without VDAC. Nat Cell Biol 9:487–489

    Article  CAS  PubMed  Google Scholar 

  • Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12:931–947

    Article  CAS  PubMed  Google Scholar 

  • Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zörnig M, MacLeod AR, Spector DL, Diederichs S (2013a) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189

    Article  CAS  PubMed  Google Scholar 

  • Gutschner T, Hämmerle M, Diederichs S (2013b) MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med 91:791–801

    Article  CAS  PubMed  Google Scholar 

  • Hervouet E, Cizkova A, Demont J, Vojtiskova A, Pecina P, Franssen-van Hal NLW, Keijer J, Simonnet H, Ivanek R, Kmoch S, Godinot C, Houstek J (2008) HIF and reactive oxygen species regulate oxidative phosphorylation in cancer. Carcinogenesis 29:1528–1537

    Article  CAS  PubMed  Google Scholar 

  • Hock MB, Kralli A (2009) Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 71:177–203

    Article  CAS  PubMed  Google Scholar 

  • Hon CC, Ramilowski JA, Harshbarger J, Bertin N, Rackham O, Gough J, Denisenko E, Schmeier S, Poulsen TM, Severin J, Lizio M, Kawaji H, Kasukawa T, Itoh M, Burroughs AM, Noma S, Djebali S, Alam T, Medvedeva YA, Testa AC, Lipovich L, Yip CW, Abugessaisa I, Mendez M, Hasegawa A, Tang D, Lassmann T, Heutink P, Babina M, Wells CA, Kojima S, Nakamura Y, Suzuki H, Daub CO, de Hoon MJ, Arner E, Hayashizaki Y, Carninci P, Forrest AR (2017) An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 543:199–204

    Article  CAS  PubMed  Google Scholar 

  • Hu W, Alvarez-Dominguez JR, Lodish HF (2012) Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Rep 13:971–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu M, Crawford SA, Henstridge DC, Ng IH, Boey EJ, Xu Y, Febbraio MA, Jans DA, Bogoyevitch MA (2013) p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival. Biochem J 453:381–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21:1253–1261

    Article  CAS  PubMed  Google Scholar 

  • Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, Poliakov A, Cao X, Dhanasekaran SM, Wu YM, Robinson DR, Beer DG, Feng FY, Iyer HK, Chinnaiyan AM (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 47:199–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S (2013) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32:1616–1625

    Article  CAS  PubMed  Google Scholar 

  • Kim KM, Noh JH, Abdelmohsen K, Gorospe M (2017) Mitochondrial noncoding RNA transport. BMB Rep 50:164–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinnally KW, Antonsson B (2007) A tale of two mitochondrial channels, MAC and PTP, in apoptosis. Apoptosis 12:857–868

    Article  CAS  PubMed  Google Scholar 

  • Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163

    Article  CAS  PubMed  Google Scholar 

  • Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, Lemesle G, de Groote P, Pinet F, Thum T (2014) Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res 114:1569–1575

    Article  CAS  PubMed  Google Scholar 

  • Landerer E, Villegas E, Burzio VA, Oliveira L, Villota C, Lopez C, Restovic F, Martinez R, Castillo O, Burzio LO (2011) Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells. Cell Oncol 34:297–305

    Article  CAS  Google Scholar 

  • Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, Radaelli E, Eyckerman S, Leonelli C, Vanderheyden K, Rogiers A, Hermans E, Baatsen P, Aerts S, Amant F, Van Aelst S, van den Oord J, de Strooper B, Davidson I, Lafontaine DL, Gevaert K, Vandesompele J, Mestdagh P, Marine JC (2016) Melanoma addiction to the long non-coding RNA SAMMSON. Nature 531:518–522

    Article  CAS  PubMed  Google Scholar 

  • Li X, Wang H, Yao B, Xu W, Chen J, Zhou X (2016) lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy. Sci Rep 6:e36340

    Article  Google Scholar 

  • Liang WC, Fu WM, Wong CW, Wang Y, Wang WM, Hu GX, Zhang L, Xiao LJ, Wan DCC, Zhang JF, Waye MMY (2015) The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. Oncotarget 6:22513–22525

    PubMed  PubMed Central  Google Scholar 

  • Liesa M, Palacín M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89:799–845

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Wang C, Wang J, Huang H (2016a) miR-1297 promotes cell proliferation by inhibiting RB1 in liver cancer. Oncol Lett 12:5177–5182

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu S, Xu B, Yan D (2016b) Enhanced expression of long non-coding RNA Sox2ot promoted cell proliferation and motility in colorectal cancer. Minerva Med 107:279–286

    PubMed  Google Scholar 

  • Lobos-Gonzalez L, Silva V, Araya M, Restovic F, Echenique J, Oliveira-Cruz L, Fitzpatrick C, Briones M, Villegas J, Villota C, Vidaurre S, Borgna V, Socias M, Valenzuela S, Lopez C, Socias T, Varas M, Diaz J, Burzio LO, Burzio V (2016) Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. Oncotarget 7:58331–58350

    Article  PubMed  PubMed Central  Google Scholar 

  • Long J, Badal SS, Ye Z, Wang Y, Ayanga BA, Galvan DL, Green NH, Chang BH, Overbeek PA, Danesh FR (2016) Long noncoding RNA Tug1 regulates mitochondrial bioenergetics in diabetic nephropathy. J Clin Investig 126:4205–4218

    Article  PubMed  PubMed Central  Google Scholar 

  • Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E (2007) The H19 non-coding RNA is essential for human tumor growth. PLoS One 2:e845

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsui M, Corey DR (2017) Non-coding RNAs as drug targets. Nat Rev 16:167–179

    CAS  Google Scholar 

  • Mendell JT, Olson EN (2012) MicroRNAs in stress signaling and human disease. Cell 148:1172–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, Filipovska A, Mattick JS (2011) The human mitochondrial transcriptome. Cell 146:645–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita M, Gravel SP, Hulea L, Larsson O, Pollak M, St-Pierre J, Topisirovic I (2015) mTOR coordinates protein synthesis, mitochondrial activity and proliferation. Cell Cycle 14:473–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishida-Aoki N, Mori H, Kuroda K, Ueda M (2015) Activation of the mitochondrial signaling pathway in response to organic solvent stress in yeast. Curr Genet 61:153–164

    Article  CAS  PubMed  Google Scholar 

  • Noh JH, Kim KM, Abdelmohsen K, Yoon JH, Panda AC, Munk R, Kim J, Curtis J, Moad CA, Wohler CM, Indig FE, de Paula W, Dudekula DB, De S, Piao Y, Yang X, Martindale JL, de Cabo R, Gorospe M (2016) HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev 30:1–16

    Article  Google Scholar 

  • Noutsopoulos D, Markopoulos G, Vartholomatos G, Kolettas E, Kolaitis N, Tzavaras T (2010) VL30 retrotransposition signals activation of a caspase-independent and p53-dependent death pathway associated with mitochondrial and lysosomal damage. Cell Res 20:553–562

    Article  CAS  PubMed  Google Scholar 

  • Pietraforte D, Malorni W (2014) Focusing at the double-edged sword of redox imbalance: signals for cell survival or for cell death? Antioxid Redox Signal 21:52–55

    Article  CAS  PubMed  Google Scholar 

  • Rackham O, Shearwood A-MJ, Mercer TR, Davies SMK, Mattick JS, Filipovska A (2011) Long noncoding RNA are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA 17:2058–2093

    Article  Google Scholar 

  • Raveh E, Matouk IJ, Gilon M, Hochberg A (2015) The H19 Long non-coding RNA in cancer initiation, progression and metastasis—a proposed unifying theory. Mol Cancer 14:e184

    Article  Google Scholar 

  • Richler C, Soreq H, Wahrman J (1992) X-inactivation in mammalian testis is correlated with inactive X-specific transcription. Nat Genet 2:192–195

    Article  CAS  PubMed  Google Scholar 

  • Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivadeneira DB, Caino MC, Seo JH, Angelin A, Wallace DC, Languino LR, Altieri DC (2015) Survivin promotes oxidative phosphorylation, subcellular mitochondrial repositioning, and tumor cell invasion. Sci Signal 8:ra80

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodríguez-Enríquez S, Vital-González PA, Flores-Rodríguez FL, Marín-Hernández A, Ruiz-Azuara L, Moreno-Sánchez R (2006) Control of cellular proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells. Toxicol Appl Pharmacol 215:208–217

    Article  PubMed  Google Scholar 

  • Semenza GL (2011) Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta 1813:1263–1268

    Article  CAS  PubMed  Google Scholar 

  • Shoshan-Barmatz V, Golan M (2012) Mitochondrial VDAC1: function in cell life and death and a target for cancer therapy. Curr Med Chem 19:714–735

    Article  CAS  PubMed  Google Scholar 

  • Spitale RC, Tsai MC, Chang HY (2011) RNA templating the epigenome: long noncoding RNAs as molecular scaffolds. Epigenetics 6:539–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srikantan S, Gorospe M (2012) HuR function in disease. Front Biosci 17:189–205

    Article  CAS  Google Scholar 

  • Trimarchi T, Bilal E, Ntziachristos P, Fabbri G, Dalla-Favera R, Tsirigos A, Aifantis I (2014) Genome-wide mapping and characterization of Notch-regulated long noncoding RNAs in acute leukemia. Cell 158:593–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vafa O, Wade M, Kern S, Beeche M, Pandita TK, Hampton GM, Wahl GM (2002) c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 9:1031–1044

    Article  CAS  PubMed  Google Scholar 

  • Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vidaurre S, Fitzpatrick C, Burzio VA, Briones M, Villota C, Villegas J, Echenique J, Oliveira-Cruz L, Araya M, Borgna V, Socías T, Lopez C, Avila R, Burzio LO (2014) Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy. J Biol Chem 289:27182–27198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villegas J, Burzio V, Villota C, Landerer E, Martinez R, Santander M, Martinez R, Pinto R, Vera MI, Boccardo E, Villa LL, Burzio LO (2007) Expression of a novel non-coding mitochondrial RNA in human proliferating cells. Nucl Acids Res 35:7336–7347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volders PJ, Verheggen K, Menschaert G, Vandepoele K, Martens L, Vandesompele J, Mestdagh P (2015) An update on LNCipedia: a database for annotated human lncRNA sequences. Nucl Acids Res 43:4363–4364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagener J (2016) Regulation of mitochondrial inner membrane fusion: divergent evolution with similar solutions? Curr Genet 62:291–294

    Article  CAS  PubMed  Google Scholar 

  • Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci 92:5510–5514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY (2011) A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472:120–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang K, Long B, Zhou LY, Liu F, Zhou QY, Liu CY, Fan YY, Li PF (2013) CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun 5:e3596

    Google Scholar 

  • Wei X, Wang C, Ma C, Sun W, Li H, Cai Z (2016) Long noncoding RNA ANRIL is activated by hypoxia-inducible factor-1α and suppresses cell apoptosis upon hypoxia. Cancer Cell Int 16:e73

    Article  Google Scholar 

  • Winkle M, van den Berg A, Tayari M, Sietzema J, Terpstra M, Kortman G, de Jong D, Visser L, Diepstra A, Kok K, Kluiver J (2015) Long noncoding RNAs as a novel component of the Myc transcriptional network. FASEB J 29:2338–2346

    Article  CAS  PubMed  Google Scholar 

  • Wu H, Sun H, Liang X, Lima WF, Crooke ST (2013) Human RNase H1 is associated with protein P32 and is involved in mitochondrial pre-rRNA processing. PLoS One 8:e71006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin JW, Jiang YG (2017) Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells. Exp Ther Med 13:1225–1234

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu R, Mao Y, Chen K, He W, Shi W, Han Y (2017) The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells. Oncotarget. doi:10.18632/oncotarget.16640

    Google Scholar 

  • Yang W, Wu JM, Bi AD, Ou-Yang YC, Shen HH, Chirn GW, Zhou JH, Weiss E, Holman EP, Liao DJ (2013) Possible formation of mitochondrial-RNA containing chimeric or trimeric RNA implies a post-transcriptional and post-splicing mechanism for RNA fusion. PLoS One 8:e77016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang F, Zhang H, Mei Y, Wu M (2014) Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect. Mol Cell 53:88–100

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Chen L, Gu J, Zhang H, Yuan J, Lian Q, Lv G, Wang S, Wu Y, Yang YT, Wang D, Liu Y, Tang J, Luo G, Li Y, Hu L, Sun X, Wang D, Guo M, Xi Q, Xi J, Wang H, Zhang MQ, Lu ZJ (2017) Recurrently deregulated lncRNAs in hepatocellular carcinoma. Nat Commun 8:e14421

    Article  Google Scholar 

  • Zhang LF, Jiang S, Liu MF (2017) MicroRNA regulation and analytical methods in cancer cell metabolism. Cell Mol Life Sci 74:2929–2941

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Zhang J, Yu M, Xie Y, Huang Y, Wolff DW, Abel PW, Tu Y (2013) Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene 32:4814–4824

    Article  CAS  PubMed  Google Scholar 

  • Zheng P, Xiong Q, Wu Y, Chen Y, Chen Z, Fleming J, Gao D, Bi L, Ge F (2015) Quantitative proteomics analysis reveals novel insights into mechanisms of action of long noncoding RNA Hox transcript antisense intergenic RNA (HOTAIR) in HeLa cells. Mol Cell Proteom 14:1447–1463

    Article  CAS  Google Scholar 

  • Zhu H, Li X, Song Y, Zhang P, Xiao Y, Xing Y (2015) Long non-coding RNA ANRIL is up-regulated in bladder cancer and regulates bladder cancer cell proliferation and apoptosis through the intrinsic pathway. Biochem Biophys Res Commun 467:223–228

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory for Mitochondrial Investigations & Neuromuscular Reference Center, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Boel De Paepe

  2. Center for Medical Genetics, Cancer Research Institute Ghent, Ghent University, Ghent, Belgium

    Steve Lefever & Pieter Mestdagh

Authors
  1. Boel De Paepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steve Lefever
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pieter Mestdagh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boel De Paepe.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by M. Kupiec.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Paepe, B., Lefever, S. & Mestdagh, P. How long noncoding RNAs enforce their will on mitochondrial activity: regulation of mitochondrial respiration, reactive oxygen species production, apoptosis, and metabolic reprogramming in cancer. Curr Genet 64, 163–172 (2018). https://doi.org/10.1007/s00294-017-0744-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-017-0744-1

Keywords

search

Navigation