mir-16 microRNA precursor family

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
mir-16
RF00254.jpg
miR-16 microRNA secondary structure and sequence conservation.
Identifiers
Symbol mir-16
Rfam RF00254
miRBase family MIPF0000006
HUGO 31545
OMIM 609704
Other data
RNA type microRNA
Domain(s) Eukaryota;
SO {{{SO}}}
PDB structures PDBe

The miR-16 microRNA precursor family is a group of related small non-coding RNA genes that regulates gene expression. miR-16, miR-15, mir-195 and miR-457 are related microRNA precursor sequences from the mir-15 gene family ([1]). This microRNA family appears to be vertebrate specific and its members have been predicted or experimentally validated in a wide range of vertebrate species (MIPF0000006).

Background[edit]

The human miR-16 precursor was discovered through detailed expression profile and Karyotype analyses of patients by Calin and colleagues.[1] Karyotyping of chromosome structures from individuals with B-cell chronic lymphocytic leukaemias (B-CLL) found that more than half have alterations in the 13q14 region.[1][2] Deletions of this well characterised 1 megabase region of the genome[3][4] was also observed in approximately 50% of mantle cell lymphoma,[citation needed] up to 40% of multiple myeloma,[citation needed] and 60% of prostate cancers.[5] Comprehensive screenings of the region at the time did not provide consistent evidence of involvement from any of the known genes at the time.[3][4][6][7][8][9][10] Using CD5+ B-lymphocytes,[11] which is known to accumulate with B-CLL progression, the minimal region lost from 13q14 region was scrutinised for regulatory elements.[1] Publicly available sequence databases were used to identify a gene cluster which encodes the homologue to the human miR15 and miR16 from the Caenorhabditis elegans.[12][13][14]

Gene targets[edit]

In the original publication which identified the action of miR15 and miR16 in the development of B-CLL, Calin and colleagues proposed that miR16 could be the targets with imperfect base pairing for 14 genes.[1] Increased CD5+ B-lymphocytes in CLL suggests the miR16 may be involved in cellular differentiation.[1] In animal models single-stranded microRNA species act by binding to imperfect mRNA complements, typically to the 3' UTR,[15][16] although targets have also been observed in the coding sequence of the mRNA.[15][17] Downregulation of miR16 (as well as miR15) was observed in diffuse large B-cell lymphoma.[18] miR16 has been shown to bind to a nine base pair to a complementary sequence in the 3' UTR region of BCL2, which is an anti-apoptotic gene involved in an evolutionarily conserved pathway in programmed cell death.[19] In the nasopharyngeal carcinoma cell line, miR-16 has been shown to target the 3' UTR of vascular endothelial growth factor (VEGF) and repress the expression of VEGF, which is an important angiogenic factor.[20][21]

Clinical relevance[edit]

Altered expression of microRNA-16 has been observed in cancer,[22][23][24] including malignancies of the breast,[25] colon[26][27], brain[28][29] , lung[30], lymphatic system[1][18][31][32], ovaries[33], pancreas[34] , prostate[35] and stomach.[36] This difference in expression levels can be used distinguish between cancerous and healthy tissues and to determine clinical prognosis.[27][37][38] The fact that pathology is associated with a different expression profile has led to the proposal that disease specific biomarkers can provide potential targets for directed clinical intervention.[39] More recently, there is evidence that in colorectal cancer that the efficacy of treatment with the monoclonal antibody cetuximab can be assessed by the expression pattern of colorectal carcinoma after therapy.[40]

miR-16 and miR-15a are clustered within a 0.5 kbp region in Chromosome 13 (13q14) in humans, a chromosomal region shown to be deleted or down-regulated in approximately more than half of B-CLL,[1] the most prevalent form of leukemia in adults.[41] It has been also shown that patients with chronic lymhocytic leukemia harbor mutations of miR-15-16 cluster.[42] Carcinogenesis is a gradual process, involving multiple genetic mutations, thus every patient with malignancy presents with a heterogeneous population of cells. The fact that mir-16 microRNA loss is observed in a large proportion of cells indicates the change occurred early in cancer development[23] and a target for therapeutic intervention.

References[edit]

  1. ^ a b c d e f g Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002). "Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia". Proc Natl Acad Sci USA. 99 (24): 15524–15529. doi:10.1073/pnas.242606799. PMC 137750Freely accessible. PMID 12434020. 
  2. ^ Coll-Mulet L, Gil J (2009). "Genetic alterations in chronic lymphocytic leukaemia". Clin Transl Oncol. 11 (4): 194– 198. doi:10.1007/s12094-009-0340-z. PMID 19380295. 
  3. ^ a b Bullrich F, Fujii H, Calin G, Mabuchi H, Negrini M, Pekarsky Y, Rassenti L, Alder H, Reed JC, Keating MJ, Kipps TJ, Croce C, M. (2001). "Characterization of the 13q14 tumor suppressor locus in CLL: identification of ALT1, an alternative splice variant of the LEU2 gene". Cancer Res. 61 (18): 6640– 6648. PMID 11559527. 
  4. ^ a b Migliazza A, Bosch F, Komatsu H, Cayanis E, Martinotti S, Toniato E, Guccione E, Qu X, Chien M, Murty VV, Gaidano G, Inghirami G, Zhang P, Fischer S, Kalachikov SM, Russo J, Edelman I, Efstratiadis A, Dalla-Favera R (2001). "Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia". Blood. 97 (7): 2098– 2104. doi:10.1182/blood.V97.7.2098. PMID 11264177. 
  5. ^ Dong JT, Boyd JC, Frierson HF Jr (2001). "Loss of heterozygosity at 13q14 and 13q21 in high grade, high stage prostate cancer". Prostate. 49 (3): 166– 171. doi:10.1002/pros.1131. PMID 11746261. 
  6. ^ Liu Y, Corcoran M, Rasool O, Ivanova G, Ibbotson R, Grander D, Iyengar A, Baranova A, Kashuba V, Merup M, Wu XS, Gardiner A, Mullenbach R, Poltaraus A, Hultstrom AL, Juliusson G, Chapman R, Tiller M, Cotter F, Gahrton G, Yankovsky N, Zabarovsky E, Einhorn S, Oscier D (1997). "Cloning of two candidate tumor suppressor genes within a 10 kb region on chromosome 13q14, frequently deleted in chronic lymphocytic leukemia". Oncogene. 15 (20): 2463– 2473. doi:10.1038/sj.onc.1201643. PMID 9395242. 
  7. ^ Mabuchi H, Fujii H, Calin G, Alder H, Negrini M, Rassenti L, Kipps TJ, Bullrich F, Croce CM (2001). "Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell chronic lymphocytic leukemia". Cancer Res. 61 (7): 2870– 2877. PMID 11306461. 
  8. ^ Rondeau G, Moreau I, Bézieau S, Petit JL, Heilig R, Fernandez S, Pennarun E, Myers JS, Batzer MA, Moisan JP, Devilder MC (2001). "Comprehensive analysis of a large genomic sequence at the putative B-cell chronic lymphocytic leukaemia (B-CLL) tumour suppresser gene locus". Mutat Res. 458 (3–4): 55–70. doi:10.1016/S0027-5107(01)00219-6. PMID 11691637. 
  9. ^ Wolf S, Mertens D, Schaffner C, Korz C, Dohner H, Stilgenbauer S, Lichter P (2001). "B-cell neoplasia associated gene with multiple splicing (BCMS): the candidate B-CLL gene on 13q14 comprises more than 560 kb covering all critical regions". Hum Mol Genet. 10 (12): 1275– 1285. doi:10.1093/hmg/10.12.1275. PMID 11406609. 
  10. ^ Rowntree C, Duke V, Panayiotidis P, Kotsi P, Palmisano GL, Hoffbrand AV, Foroni L (2002). "Deletion analysis of chromosome 13q14.3 and characterisation of an alternative splice form of LEU1 in B cell chronic lymphocytic leukemia". Leukemia. 16 (17): 1267– 1275. doi:10.1038/sj.leu.2402551. PMID 12094250. 
  11. ^ Caligaris-Cappio F, Hamblin TJ (1999). "B-cell chronic lymphocytic leukemia: a bird of a different feather". J Clin Oncol. 17 (1): 399– 408. PMID 10458259. 
  12. ^ Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001). "Identification of novel genes coding for small expressed RNAs". Science. 294 (5543): 853– 858. doi:10.1126/science.1064921. PMID 11679670. 
  13. ^ Lau NC, Lim LP, Weinstein EG, Bartel DP (2001). "An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans". Science. 294 (5543): 858– 862. doi:10.1126/science.1065062. PMID 11679671. 
  14. ^ Lee RC, Ambros V (2001). "An extensive class of small RNAs in Caenorhabditis elegans". Science. 294 (5543): 862– 864. doi:10.1126/science.1065329. PMID 11679672. 
  15. ^ a b Lewis BP, Burge CB, Bartel DP (2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets". Cell. 120 (1): 15– 20. doi:10.1016/j.cell.2004.12.035. PMID 15652477. 
  16. ^ Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M (2005). "Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals". Nature. 434 (7031): 338– 345. doi:10.1038/nature03441. PMC 2923337Freely accessible. PMID 15735639. 
  17. ^ Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I (2008). "MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation". Nature. 455 (7216): 1124– 1128. doi:10.1038/nature07299. PMID 18806776. 
  18. ^ a b Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE (2004). "Accumulation of miR-155 and BIC RNA in human B-cell lymphoma". Proc Natl Acad Sci U S A. 102 (10): 3627–3632. doi:10.1073/pnas.0500613102. PMC 552785Freely accessible. PMID 15738415. 
  19. ^ Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005). "miR-15 and miR-16 induce apoptosis by targeting BCL2". Proc Natl Acad Sci U S A. 102 (39): 13944– 13949. doi:10.1073/pnas.0506654102. PMC 1236577Freely accessible. PMID 16166262. 
  20. ^ Hua Z, Lv Q, Ye W, Wong CK, Cai G, Gu D, Ji Y, Zhao C, Wang J, Yang BB, Zhang Y (Dec 27, 2006). "MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia". PLOS ONE. 1 (1): e116. doi:10.1371/journal.pone.0000116. PMC 1762435Freely accessible. PMID 17205120. 
  21. ^ Ye W, Lv Q, Wong CK, Hu S, Fu C, Hua Z, Cai G, Li G, Yang BB, Zhang Y (Mar 5, 2008). "The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA-mediated gene regulation". PLOS ONE. 3 (3): e1719. doi:10.1371/journal.pone.0001719. PMC 2248708Freely accessible. PMID 18320040. 
  22. ^ Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005). "MicroRNA expression profiles classify human cancers". Nature. 435 (7043): 834–838. doi:10.1038/nature03702. PMID 15944708. 
  23. ^ a b Croce CM. (2009). "Causes and consequences of microRNA dysregulation in cancer". Nat Rev Genet. 10 (10): 704–714. doi:10.1038/nrg2634. PMC 3467096Freely accessible. PMID 19763153. 
  24. ^ Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM (2004). "Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers". Proc Natl Acad Sci U S A. 101 (9): 2999– 3004. doi:10.1073/pnas.0307323101. PMC 365734Freely accessible. PMID 14973191. 
  25. ^ Rivas MA, Venturutti L, Huang YW, Schillaci R, Huang TH, Elizalde PV (2012). "Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic signaling contributes to breast cancer development". Breast Cancer Res. 14 (3): R77. doi:10.1186/bcr3187. PMC 3446340Freely accessible. PMID 22583478. 
  26. ^ Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP, James RJ (2003). "Reduced accumulation of specific microRNAs in colorectal neoplasia". Mol Cancer Res. 1 (12): 882–891. PMID 14573789. 
  27. ^ a b Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC (2008). "MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma". JAMA. 299 (4): 425– 436. doi:10.1001/jama.299.4.425. PMC 2614237Freely accessible. PMID 18230780. 
  28. ^ Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG (2005). "Extensive modulation of a set of microRNAs in primary glioblastoma". Biochem Biophys Res Commun. 334 (4): 1351– 1358. doi:10.1016/j.bbrc.2005.07.030. PMID 16039986. 
  29. ^ Chan JA, Krichevsky AM, Kosik KS (2007). "MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells". Cancer Res. 65 (14): 6029– 6033. doi:10.1158/0008-5472.CAN-05-0137. PMID 16024602. 
  30. ^ Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T (2004). "Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival". Cancer Res. 64 (11): 3753–3756. doi:10.1158/0008-5472.CAN-04-0637. PMID 15172979. 
  31. ^ Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A (2004). "High expression of precursor microRNA-155/BIC RNA in children with Burkitt's lymphoma". Genes Chromosomes Cancer. 39 (2): 167–169. doi:10.1002/gcc.10316. PMID 14695998. 
  32. ^ Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M (2004). "Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant Lymphoma". Cancer Res. 64 (9): 3087– 3095. doi:10.1158/0008-5472.CAN-03-3773. PMID 15126345. 
  33. ^ Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM (2007). "MicroRNA signatures in human ovarian cancer". Cancer Res. 67 (8): 8699– 8707. doi:10.1158/0008-5472.CAN-07-1936. PMID 17875710. 
  34. ^ Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM (2007). "MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis". JAMA. 297 (17): 1901– 1908. doi:10.1001/jama.297.17.1901. PMID 17473300. 
  35. ^ Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, Bartucci M, Muto G, Peschle C, De Maria R (2008). "The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities". Nat Med. 14 (11): 1271– 1277. doi:10.1038/nm.1880. PMID 18931683. 
  36. ^ Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu CG, Negrini M, Cavazzini L, Volinia S, Alder H, Ruco LP, Baldassarre G, Croce CM, Vecchione A (2008). "MicroRNA signatures in human ovarian cancer". Cancer Cell. 13 (3): 272– 286. doi:10.1016/j.ccr.2008.02.013. PMID 18328430. 
  37. ^ Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC (2006). "Unique microRNA molecular profiles in lung cancer diagnosis and prognosis". Cancer Cell. 9 (3): 189– 198. doi:10.1016/j.ccr.2006.01.025. PMID 16530703. 
  38. ^ Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005). "A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia". N Engl J Med. 353 (17): 1793– 1801. doi:10.1056/NEJMoa050995. PMID 16251535. 
  39. ^ Cho WC. (2010). "MicroRNAs as therapeutic targets for lung cancer". Expert Opin Ther Targets. 14 (10): 1005–1008. doi:10.1517/14728222.2010.522399. PMID 20854177. 
  40. ^ Ragusa M, Majorana A, Statello L, Maugeri M, Salito L, Barbagallo D, Guglielmino MR, Duro LR, Angelica R, Caltabiano R, Biondi A, Di Vita M, Privitera G, Scalia M, Cappellani A, Vasquez E, Lanzafame S, Basile F, Di Pietro C, Purrello M (2010). "Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment". Mol Cancer Ther. 9 (12): 3396–409. doi:10.1158/1535-7163.MCT-10-0137. PMID 20881268. 
  41. ^ Döhner H; Stilgenbauer S. Benner A; Leupolt E; Krober A; Bullinger L; Dohner K; Bentz M; Lichter P. (2000). "Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia". N Engl J Med. 343 (26): 1910–1916. doi:10.1056/NEJM200012283432602. PMID 11136261. 
  42. ^ Kminkova J, Mraz M, Zaprazna K, Navrkalova V, Tichy B, Plevova K, Malcikova J, Cerna K, Rausch T, Benes V, Brychtova Y, Doubek M, Mayer J, Pospisilova S (2014). "Identification of novel sequence variations in microRNAs in chronic lymphocytic leukemia". Carcinogenesis. 35: 992–1002. doi:10.1093/carcin/bgt396. PMC 4004199Freely accessible. PMID 24306027. 

Further reading[edit]

External links[edit]

  1. ^ Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O (2010). "miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants". Science. 329 (5998): 1537–41. doi:10.1126/science.1193692. PMID 20847275. 
  2. ^ Zhang X, Wan G, Mlotshwa S, Vance V, Berger FG, Chen H, Lu X (2010). "Oncogenic Wip1 phosphatase is inhibited by miR-16 in the DNA damage signaling pathway". Cancer Res. 70 (18): 7176–86. doi:10.1158/0008-5472.CAN-10-0697. PMC 2940956Freely accessible. PMID 20668064. 
  3. ^ Maccani MA, Avissar-Whiting M, Banister CE, McGonnigal B, Padbury JF, Marsit CJ (2010). "Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21 and miR-146a in the placenta". Epigenetics. 5 (7): 583–9. doi:10.4161/epi.5.7.12762. PMC 2974801Freely accessible. PMID 20647767. 
  4. ^ Balakrishnan A, Stearns AT, Park PJ, Dreyfuss JM, Ashley SW, Rhoads DB, Tavakkolizadeh A (2010). "MicroRNA mir-16 is anti-proliferative in enterocytes and exhibits diurnal rhythmicity in intestinal crypts". Exp Cell Res. 316 (20): 3512–21. doi:10.1016/j.yexcr.2010.07.007. PMC 2976799Freely accessible. PMID 20633552. 
  5. ^ Xu F, Zhang X, Lei Y, Liu X, Liu Z, Tong T, Wang W (2010). "Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma". J Cell Biochem. 111 (3): 727–34. doi:10.1002/jcb.22762. PMID 20626035. 
  6. ^ Liu W, Liu C, Zhu J, Shu P, Yin B, Gong Y, Qiang B, Yuan J, Peng X (2010). "MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer's-associated pathogenesis in SAMP8 mice". Neurobiol Aging. 33: 522–534. doi:10.1016/j.neurobiolaging.2010.04.034. PMID 20619502. 
  7. ^ Yang J, Cao Y, Sun J, Zhang Y (2009). "Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells". Med Oncol. 27 (4): 1114–8. doi:10.1007/s12032-009-9344-3. PMID 19908170. 
  8. ^ Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, Calin GA, Mukherjee P (2009). "MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer". Cancer Res. 69 (23): 9090–5. doi:10.1158/0008-5472.CAN-09-2552. PMC 2859686Freely accessible. PMID 19903841. 
  9. ^ Guo CJ, Pan Q, Jiang B, Chen GY, Li DG (2009). "Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells". Apoptosis. 14 (11): 1331–40. doi:10.1007/s10495-009-0401-3. PMID 19784778. 
  10. ^ Hanlon K, Rudin CE, Harries LW (2009). Williams, Simon, ed. "Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL)". PLoS ONE. 4 (9): e7169. doi:10.1371/journal.pone.0007169. PMC 2745703Freely accessible. PMID 19779621. 
  11. ^ Takeshita F, Patrawala L, Osaki M, Takahashi RU, Yamamoto Y, Kosaka N, Kawamata M, Kelnar K, Bader AG, Brown D, Ochiya T (2010). "Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes". Mol Ther. 18 (1): 181–7. doi:10.1038/mt.2009.207. PMC 2839211Freely accessible. PMID 19738602. 
  12. ^ Lerner M, Harada M, Lovén J, Castro J, Davis Z, Oscier D, Henriksson M, Sangfelt O, Grandér D, Corcoran MM (2009). "DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1". Exp Cell Res. 315 (17): 2941–52. doi:10.1016/j.yexcr.2009.07.001. PMID 19591824. 
  13. ^ Bandi N, Zbinden S, Gugger M, Arnold M, Kocher V, Hasan L, Kappeler A, Brunner T, Vassella E (2009). "miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer". Cancer Res. 69 (13): 5553–9. doi:10.1158/0008-5472.CAN-08-4277. PMID 19549910. 
  14. ^ Aqeilan RI, Calin GA, Croce CM (2010). "miR-15a and miR-16-1 in cancer: discovery, function and future perspectives". Cell Death Differ. 17 (2): 215–20. doi:10.1038/cdd.2009.69. PMID 19498445. 
  15. ^ Tsang WP, Kwok TT (2010). "Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells". J Nutr Biochem. 21 (2): 140–6. doi:10.1016/j.jnutbio.2008.12.003. PMID 19269153. 
  16. ^ Kaddar T, Rouault JP, Chien WW, Chebel A, Gadoux M, Salles G, Ffrench M, Magaud JP (2009). "Two new miR-16 targets: caprin-1 and HMGA1, proteins implicated in cell proliferation". Biol Cell. 101 (9): 511–24. doi:10.1042/BC20080213. PMID 19250063. 
  17. ^ Guo CJ, Pan Q, Li DG, Sun H, Liu BW (2009). "miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis". J Hepatol. 50 (4): 766–78. doi:10.1016/j.jhep.2008.11.025. PMID 19232449. 
  18. ^ Kaddar T, Chien WW, Bertrand Y, Pages MP, Rouault JP, Salles G, Ffrench M, Magaud JP (2009). "Prognostic value of miR-16 expression in childhood acute lymphoblastic leukemia relationships to normal and malignant lymphocyte proliferation". Leuk Res. 33 (9): 1217–23. doi:10.1016/j.leukres.2008.12.015. PMID 19195700. 
  19. ^ Karaa ZS, Iacovoni JS, Bastide A, Lacazette E, Touriol C, Prats H (2009). "The VEGF IRESes are differentially susceptible to translation inhibition by miR-16". RNA. 15 (2): 249–54. doi:10.1261/rna.1301109. PMC 2648711Freely accessible. PMID 19144909. 
  20. ^ Shanmugam N, Reddy MA, Natarajan R (2008). "Distinct roles of heterogeneous nuclear ribonuclear protein K and microRNA-16 in cyclooxygenase-2 RNA stability induced by S100b, a ligand of the receptor for advanced glycation end products". J Biol Chem. 283 (52): 36221–33. doi:10.1074/jbc.M806322200. PMC 2606002Freely accessible. PMID 18854308. 
  21. ^ Liu Q, Fu H, Sun F, Zhang H, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008). "miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes". Nucleic Acids Res. 36 (16): 5391–404. doi:10.1093/nar/gkn522. PMC 2532718Freely accessible. PMID 18701644. 
  22. ^ Chen RW, Bemis LT, Amato CM, Myint H, Tran H, Birks DK, Eckhardt SG, Robinson WA (2008). "Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma". Blood. 112 (3): 822–9. doi:10.1182/blood-2008-03-142182. PMC 2481543Freely accessible. PMID 18483394. 
  23. ^ 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): 372–9. doi:10.1002/ijc.23501. PMID 18449891. 
  24. ^ Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM (2008). "MiR-15a and miR-16-1 cluster functions in human leukemia". Proc Natl Acad Sci U S A. 105 (13): 5166–71. doi:10.1073/pnas.0800121105. PMC 2278188Freely accessible. PMID 18362358. 
  25. ^ Scaglione BJ, Salerno E, Balan M, Coffman F, Landgraf P, Abbasi F, Kotenko S, Marti GE, Raveche ES (2007). "Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model". Br J Haematol. 139 (5): 645–57. doi:10.1111/j.1365-2141.2007.06851.x. PMC 2692662Freely accessible. PMID 17941951. 
  26. ^ Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K, Toro JR, Zenger VE, Metcalf RA, Marti GE (2007). "Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice". Blood. 109 (12): 5079–86. doi:10.1182/blood-2007-02-071225. PMC 1890829Freely accessible. PMID 17351108. 
  27. ^ Linsley PS, Schelter J, Burchard J, Kibukawa M, Martin MM, Bartz SR, Johnson JM, Cummins JM, Raymond CK, Dai H, Chau N, Cleary M, Jackson AL, Carleton M, Lim L (2007). "Transcripts targeted by the microRNA-16 family cooperatively regulate cell cycle progression". Mol Cell Biol. 27 (6): 2240–52. doi:10.1128/MCB.02005-06. PMC 1820501Freely accessible. PMID 17242205. 
  28. ^ Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC (2005). "miR-15a and miR-16-1 down-regulation in pituitary adenomas". J Cell Physiol. 204 (1): 280–5. doi:10.1002/jcp.20282. PMID 15648093.