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MicroRNAs and drug modulation in cancer: an intertwined new story

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Frontiers in Biology

Abstract

MicroRNAs (miRNAs) are endogenous small non-coding RNAs (ncRNAs) which play important regulatory roles in physiological processes such as cellular differentiation, proliferation, development, apoptosis and stem cell self-renewal. An increasing number of papers have clearly claimed their involvement in cancer, providing, in some cases, also the molecular mechanisms implicated. Several studies led to the conclusion that miRNAs can be effectively used as anticancer agents alone or in combination with existing anticancer drugs. In particular, miRNAs can be effectively used to overcome drug resistance, one of the main factors responsible for anticancer treatment insuccess. One of the main questions remains how to modulate the expression of miRNAs in cancer cells. Interestingly, a few studies have shown that the expression of miRNAs is affected by drugs (including some drugs currently used as anticancer agents), therefore providing the rationale for an intertwined scenario in which miRNAs can be modulated by drugs and, in turn, can affect drug sensitivity of cancer cells.

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References

  • Ali S, Ahmad A, Banerjee S, Padhye S, Dominiak K, Schaffert J M, Wang Z, Philip P A, Sarkar F H (2010). Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res, 70(9): 3606–3617

    Article  PubMed  CAS  Google Scholar 

  • Ambros V, Lee R C (2004). Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol Biol, 265: 131–158

    PubMed  CAS  Google Scholar 

  • Bartel D P (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2): 281–297

    Article  PubMed  CAS  Google Scholar 

  • Bommer G T, Gerin I, Feng Y, Kaczorowski A J, Kuick R, Love R E, Zhai Y, Giordano T J, Qin Z S, Moore B B, MacDougald O A, Cho K R, Fearon E R (2007). p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol, 17(15): 1298–1307

    Article  PubMed  CAS  Google Scholar 

  • Borchert G M, Lanier W, Davidson B L (2006). RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol, 13(12): 1097–1101

    Article  PubMed  CAS  Google Scholar 

  • Cai X, Hagedorn C H, Cullen B R (2004). Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 10(12): 1957–1966

    Article  PubMed  CAS  Google Scholar 

  • Carleton M, Cleary M A, Linsley P S (2007). MicroRNAs and cell cycle regulation. Cell Cycle, 6(17): 2127–2132

    Article  PubMed  CAS  Google Scholar 

  • Castellano L, Giamas G, Jacob J, Coombes R C, Lucchesi W, Thiruchelvam P, Barton G, Jiao L R, Wait R, Waxman J, Hannon G J, Stebbing J (2009). The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response. Proc Natl Acad Sci USA, 106(37): 15732–15737

    Article  PubMed  CAS  Google Scholar 

  • Chang T C, Wentzel E A, Kent O A, Ramachandran K, Mullendore M, Lee K H, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein C J, Arking D E, Beer M A, Maitra A, Mendell J T (2007). Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell, 26(5): 745–752

    Article  PubMed  CAS  Google Scholar 

  • Climent J, Dimitrow P, Fridlyand J, Palacios J, Siebert R, Albertson D G, Gray JW, Pinkel D, Lluch A, Martinez-Climent J A (2007). Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy in early breast cancer. Cancer Res, 67(2): 818–826

    Article  PubMed  CAS  Google Scholar 

  • Corney D C, Flesken-Nikitin A, Godwin A K, Wang W, Nikitin A Y (2007). MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res, 67(18): 8433–8438

    Article  PubMed  CAS  Google Scholar 

  • Corney D C, Hwang C I, Matoso A, Vogt M, Flesken-Nikitin A, Godwin A K, Kamat A A, Sood A K, Ellenson L H, Hermeking H, Nikitin A Y (2010). Frequent downregulation of miR-34 family in human ovarian cancers. Clin Cancer Res, 16(4): 1119–1128

    Article  PubMed  CAS  Google Scholar 

  • Cullen B R (2004). Transcription and processing of human microRNA precursors. Mol Cell, 16(6): 861–865

    Article  PubMed  CAS  Google Scholar 

  • Fabbri M, Ivan M, Cimmino A, Negrini M, Calin G A (2007). Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther, 7(7): 1009–1019

    Article  PubMed  CAS  Google Scholar 

  • Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y, Deguchi T, Ito M (2008). Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun, 377(1): 114–119

    Article  PubMed  CAS  Google Scholar 

  • Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu C G, Croce C M, Condorelli G (2008). MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene, 27(27): 3845–3855

    Article  PubMed  CAS  Google Scholar 

  • Georges S A, Biery M C, Kim S Y, Schelter J M, Guo J, Chang A N, Jackson A L, Carleton M O, Linsley P S, Cleary M A, Chau B N (2008). Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215. Cancer Res, 68(24): 10105–10112

    Article  PubMed  CAS  Google Scholar 

  • He L, Hannon G J (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet, 5(7): 522–531

    Article  PubMed  CAS  Google Scholar 

  • Hermeking H (2010). The miR-34 family in cancer and apoptosis. Cell Death Differ, 17(2): 193–199

    Article  PubMed  CAS  Google Scholar 

  • Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak V P, Chekhun V F, Pogribny I P (2008). Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther, 7(7): 2152–2159

    Article  PubMed  CAS  Google Scholar 

  • Kunnumakkara A B, Anand P, Aggarwal B B (2008). Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett, 269(2): 199–225

    Article  PubMed  CAS  Google Scholar 

  • Kunnumakkara A B, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal B B (2007). Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res, 67(8): 3853–3861

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Kim M, Han J, Yeom K H, Lee S, Baek S H, Kim V N (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23(20): 4051–4060

    Article  PubMed  CAS  Google Scholar 

  • Lev-Ari S, Vexler A, Starr A, Ashkenazy-Voghera M, Greif J, Aderka D, Ben-Yosef R (2007). Curcumin augments gemcitabine cytotoxic effect on pancreatic adenocarcinoma cell lines. Cancer Invest, 25(6): 411–418

    Article  PubMed  CAS  Google Scholar 

  • Lytle J R, Yario T A, Steitz J A (2007). Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci USA, 104(23): 9667–967

    Article  PubMed  CAS  Google Scholar 

  • Masri S, Liu Z, Phung S, Wang E, Yuan Y C, Chen S (2010). The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells. Breast Cancer Res Treat, 124(1): 89–99

    Article  PubMed  CAS  Google Scholar 

  • Miller T E, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro C L, Jacob S, Majumder S (2008). MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem, 283(44): 29897–29903

    Article  PubMed  CAS  Google Scholar 

  • Pasquinelli A E, Hunter S, Bracht J (2005). MicroRNAs: a developing story. Curr Opin Genet Dev, 15(2): 200–205

    Article  PubMed  CAS  Google Scholar 

  • Plasterk R H (2006). Micro RNAs in animal development. Cell, 124(5): 877–881

    Article  PubMed  CAS  Google Scholar 

  • Qin W, Shi Y, Zhao B, Yao C, Jin L, Ma J, Jin Y (2010). miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One, 5(2): e9429

    Article  PubMed  Google Scholar 

  • Sorrentino A, Liu C G, Addario A, Peschle C, Scambia G, Ferlini C (2008). Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol, 111(3): 478–486

    Article  PubMed  CAS  Google Scholar 

  • Sun M, Estrov Z, Ji Y, Coombes K R, Harris D H, Kurzrock R (2008). Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther, 7(3): 464–473

    Article  PubMed  CAS  Google Scholar 

  • Szakács G, Paterson J K, Ludwig J A, Booth-Genthe C, Gottesman MM (2006). Targeting multidrug resistance in cancer. Nat Rev Drug Discov, 5(3): 219–234

    Article  PubMed  Google Scholar 

  • 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(13): 1586–1593

    Article  PubMed  CAS  Google Scholar 

  • Vasudevan S, Tong Y, Steitz J A (2007). Switching from repression to activation: microRNAs can up-regulate translation. Science, 318(5858): 1931–1934

    Article  PubMed  CAS  Google Scholar 

  • Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D (2008). miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer, 123(2): 372–379

    Article  PubMed  CAS  Google Scholar 

  • Xin F, Li M, Balch C, Thomson M, Fan M, Liu Y, Hammond S M, Kim S, Nephew K P (2009). Computational analysis of microRNA profiles and their target genes suggests significant involvement in breast cancer antiestrogen resistance. Bioinformatics, 25(4): 430–434

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Kong W, He L, Zhao J J, O’Donnell J D, Wang J, Wenham RM, Coppola D, Kruk P A, Nicosia S V, Cheng J Q (2008). MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res, 68(2): 425–433

    Article  PubMed  CAS  Google Scholar 

  • Zheng T, Wang J, Chen X, Liu L (2010). Role of microRNA in anticancer drug resistance. Int J Cancer, 126(1): 2–10

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Muller Fabbri.

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Fanini, F., Vannini, I. & Fabbri, M. MicroRNAs and drug modulation in cancer: an intertwined new story. Front. Biol. 6, 351–356 (2011). https://doi.org/10.1007/s11515-011-1115-9

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  • DOI: https://doi.org/10.1007/s11515-011-1115-9

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