Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2007

Open Access 01-12-2007 | Review

OncomiRs: the discovery and progress of microRNAs in cancers

Author: William CS Cho

Published in: Molecular Cancer | Issue 1/2007

Login to get access

Abstract

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of about 22 nucleotides in length that function as posttranscriptional gene regulators. They are deemed to play a crucial role in the initiation and progression of human cancer, and those with a role in cancer are designated as oncogenic miRNAs (oncomiRs). For example, miR-15 and miR-16 induce apoptosis by targeting Bcl2. miRNAs from the miR-17-92 cluster modulate tumor formation and function as oncogenes by influencing the translation of E2F1 mRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10-dependent activation of PI 3-kinase signaling. miR-34a acts as a suppressor of neuroblastoma tumorigenesis by targeting the mRNA encoding E2F3 and reducing E2F3 protein levels. The chromosomal translocations associating with human tumors disrupt the repression of High mobility group A2 by let-7 miRNA. In addition, the oncomiRs expression profiling of human malignancies has also identified a number of diagnostic and prognostic cancer signatures. This article introduces the roles of oncomiRs in neoplasm development, progression, diagnosis, prognostication, as well as their mechanism of actions on target mRNAs and the functional outcomes of their actions on mRNAs. The paper ends with a brief perspective to the future of oncomiRs.
Literature
1.
Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T: Identification of novel genes coding for small expressed RNAs. Science. 2001, 294: 853-858. 10.1126/science.1064921CrossRefPubMed
2.
Meltzer PS: Cancer genomics: small RNAs with big impacts. Nature. 2005, 435: 745-746. 10.1038/435745aCrossRefPubMed
3.
Lee RC, Feinbaum RL, Ambros V: The C.elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993, 75: 843-854. 10.1016/0092-8674(93)90529-YCrossRefPubMed
4.
Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E: Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005, 120: 21-24. 10.1016/j.cell.2004.12.031CrossRefPubMed
5.
Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005, 120: 15-20. 10.1016/j.cell.2004.12.035CrossRefPubMed
6.
7.
Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6: 857-866. 10.1038/nrc1997CrossRefPubMed
8.
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: Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002, 99: 15524-15529. 10.1073/pnas.242606799PubMedCentralCrossRefPubMed
9.
Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004, 101: 2999-3004. 10.1073/pnas.0307323101PubMedCentralCrossRefPubMed
10.
Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, degli Uberti EC: miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 2005, 204: 280-285. 10.1002/jcp.20282CrossRefPubMed
11.
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: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005, 102: 13944-13949. 10.1073/pnas.0506654102PubMedCentralCrossRefPubMed
12.
Garzon R, Pichiorri F, Palumbo T, Visentini M, Aqeilan R, Cimmino A, Wang H, Sun H, Volinia S, Alder H, Calin GA, Liu CG, Andreeff M, Croce CM: MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia. Oncogene. 2007, 26: 4148-4157. 10.1038/sj.onc.1210186CrossRefPubMed
13.
He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 2005, 435: 828-833. 10.1038/nature03552PubMedCentralCrossRefPubMed
14.
O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005, 435: 839-843. 10.1038/nature03677CrossRefPubMed
15.
Woods K, Thomson JM, Hammond SM: Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem. 2007, 282: 2130-2134. 10.1074/jbc.C600252200CrossRefPubMed
16.
Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005, 65: 9628-9632. 10.1158/0008-5472.CAN-05-2352CrossRefPubMed
17.
Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, Osada H, Takahashi T: Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007, 26: 6099-105. 10.1038/sj.onc.1210425CrossRefPubMed
18.
Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65: 7065-7070. 10.1158/0008-5472.CAN-05-1783CrossRefPubMed
19.
Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY: miR-21 -mediated tumor growth. Oncogene. 2007, 26: 2799-2803. 10.1038/sj.onc.1210083CrossRefPubMed
20.
Zhu S, Si ML, Wu H, Mo YY: MicroRNA-21 Targets the tumor suppressor gene Tropomyosin 1 (TPM1). J Biol Chem. 2007, 282: 14328-14336. 10.1074/jbc.M611393200CrossRefPubMed
21.
Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, Jiang J, Schmittgen TD, Patel T: Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006, 130: 2113-2129. 10.1053/j.gastro.2006.02.057CrossRefPubMed
22.
Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O'brien C, Rose B: MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun. 2007, 358: 12-17. 10.1016/j.bbrc.2007.03.201CrossRefPubMed
23.
Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, Croce CM: Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)- miR155 transgenic mice. Proc Natl Acad Sci USA. 2006, 103: 7024-7029. 10.1073/pnas.0602266103PubMedCentralCrossRefPubMed
24.
Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, Castellano L, Magrelli A, Citarella F, Messina M, Maggio R, Peragine N, Santangelo S, Mauro FR, Landgraf P, Tuschl T, Weir DB, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Guarini A, Foa R, Macino G: Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007, 109: 4944-4951. 10.1182/blood-2006-12-062398CrossRefPubMed
25.
Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006, 24: 4677-4684. 10.1200/JCO.2005.05.5194CrossRefPubMed
26.
Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, Liuzzi F, Lulli V, Morsilli O, Santoro S, Valtieri M, Calin GA, Liu CG, Sorrentino A, Croce CM, Peschle C: MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA. 2005, 102: 18081-18086. 10.1073/pnas.0506216102PubMedCentralCrossRefPubMed
27.
He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 2005, 102: 19075-19080. 10.1073/pnas.0509603102PubMedCentralCrossRefPubMed
28.
Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, Croce CM, Fusco A: MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006, 13: 497-508. 10.1677/erc.1.01209CrossRefPubMed
29.
Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG: Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005, 334: 1351-1358. 10.1016/j.bbrc.2005.07.030CrossRefPubMed
30.
Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM: Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006, 66: 11590-11593. 10.1158/0008-5472.CAN-06-3613CrossRefPubMed
31.
32.
Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M, Garcia-Foncillas J: Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer. 2006, 5: 29. 10.1186/1476-4598-5-29PubMedCentralCrossRefPubMed
33.
Akao Y, Nakagawa Y, Naoe T: MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep. 2006, 16: 845-850.PubMed
34.
Laneve P, Di Marcotullio L, Gioia U, Fiori ME, Ferretti E, Gulino A, Bozzoni I, Caffarelli E: The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proc Natl Acad Sci USA. 2007, 104: 7957-7962. 10.1073/pnas.0700071104PubMedCentralCrossRefPubMed
35.
Chen Y, Stallings RL: Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007, 67: 976-983. 10.1158/0008-5472.CAN-06-3667CrossRefPubMed
36.
Welch C, Chen Y, Stallings RL: MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007, 26: 5017-5022. 10.1038/sj.onc.1210293CrossRefPubMed
37.
Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007, 26: 745-752. 10.1016/j.molcel.2007.05.010PubMedCentralCrossRefPubMed
38.
Nervi C, Fazi F, Rosa A, Fatica A, Bozzoni I: Emerging role for microRNAs in acute promyelocytic leukemia. Curr Top Microbiol Immunol. 2007, 313: 73-84.PubMed
39.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 2005, 120: 635-647. 10.1016/j.cell.2005.01.014CrossRefPubMed
40.
Akao Y, Nakagawa Y, Naoe T: let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull. 2006, 29: 903-906. 10.1248/bpb.29.903CrossRefPubMed
41.
Meng F, Henson R, Wehbe-Janek H, Smith H, Ueno Y, Patel T: The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes. J Biol Chem. 2007, 282: 8256-8264. 10.1074/jbc.M607712200CrossRefPubMed
42.
Brueckner B, Stresemann C, Kuner R, Mund C, Musch T, Meister M, Sultmann H, Lyko F: The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 2007, 67: 1419-1423. 10.1158/0008-5472.CAN-06-4074CrossRefPubMed
43.
Mayr C, Hemann MT, Bartel DP: Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007, 315: 1576-1579. 10.1126/science.1137999PubMedCentralCrossRefPubMed
44.
45.
Hebert C, Norris K, Scheper MA, Nikitakis N, Sauk JJ: High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer. 2007, 6: 5. 10.1186/1476-4598-6-5PubMedCentralCrossRefPubMed
46.
Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H: Stem cell division is regulated by the microRNA pathway. Nature. 2005, 435: 974-978. 10.1038/nature03816CrossRefPubMed
47.
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: MicroRNA expression profiles classify human cancers. Nature. 2005, 435: 834-838. 10.1038/nature03702CrossRefPubMed
48.
Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, Calin GA, Negrini M, Croce CM, Degli Uberti EC: Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas. J Cell Physiol. 2007, 210: 370-377. 10.1002/jcp.20832CrossRefPubMed
49.
Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD: Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007, 120: 1046-1054. 10.1002/ijc.22394PubMedCentralCrossRefPubMed
50.
Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004, 64: 3753-3756. 10.1158/0008-5472.CAN-04-0637CrossRefPubMed
51.
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: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9: 189-198. 10.1016/j.ccr.2006.01.025CrossRefPubMed
52.
Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007, 297: 1901-1908. 10.1001/jama.297.17.1901CrossRefPubMed
53.
54.
Cho WC, Cheng CH: Oncoproteomics: current trends and future perspectives. Expert Rev Proteomics. 2007, 4: 401-410. 10.1586/14789450.4.3.401CrossRefPubMed
55.
Cho WC: A future of cancer prevention and cures: highlights of the Centennial Meeting of the American Association for Cancer Research. Ann Oncol. 2007, doi:10.1093/annonc/mdm335,
Metadata
Title
OncomiRs: the discovery and progress of microRNAs in cancers
Author
William CS Cho
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2007
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-6-60

Other articles of this Issue 1/2007

Molecular Cancer 1/2007 Go to the issue

Short communication

The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells

Research

Sodium Ascorbate induces apoptosis in neuroblastoma cell lines by interfering with iron uptake

Research

hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands

Research

Human periostin gene expression in normal tissues, tumors and melanoma: evidences for periostin production by both stromal and melanoma cells

Research

DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets

Research

O 6 -methylguanine-DNA methyltransferase is downregulated in transformed astrocyte cells: implications for anti-glioma therapies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits