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[Cancer Research 64, 3753-3756, June 1, 2004]
© 2004 American Association for Cancer Research

Advances in Brief

Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival

Junichi Takamizawa1,4, Hiroyuki Konishi1, Kiyoshi Yanagisawa1, Shuta Tomida1, Hirotaka Osada1, Hideki Endoh3, Tomoko Harano1, Yasushi Yatabe2, Masato Nagino4, Yuji Nimura4, Tetsuya Mitsudomi3 and Takashi Takahashi1

1 Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan; Departments of 2 Anatomic and Molecular Diagnostic Pathology and 3 Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan; 4 Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

In this study, we report for the first time reduced expression of the let-7 microRNA in human lung cancers. Interestingly, 143 lung cancer cases that had undergone potentially curative resection could be classified into two major groups according to let-7 expression in unsupervised hierarchical analysis, showing significantly shorter survival after potentially curative resection in cases with reduced let-7 expression (P = 0.0003). Multivariate COX regression analysis showed this prognostic impact to be independent of disease stage (hazard ratio = 2.17; P = 0.009). In addition, overexpression of let-7 in A549 lung adenocarcinoma cell line inhibited lung cancer cell growth in vitro. This study represents the first report of reduced expression of let-7 and the potential clinical and biological effects of such a microRNA alteration.




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MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN
Cancer Res., January 15, 2008; 68(2): 425 - 433.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
J. Jiang, Y. Gusev, I. Aderca, T. A. Mettler, D. M. Nagorney, D. J. Brackett, L. R. Roberts, and T. D. Schmittgen
Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival
Clin. Cancer Res., January 15, 2008; 14(2): 419 - 427.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
Y. Guo, Z. Chen, L. Zhang, F. Zhou, S. Shi, X. Feng, B. Li, X. Meng, X. Ma, M. Luo, et al.
Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma
Cancer Res., January 1, 2008; 68(1): 26 - 33.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. B. Weidhaas, I. Babar, S. M. Nallur, P. Trang, S. Roush, M. Boehm, E. Gillespie, and F. J. Slack
MicroRNAs as Potential Agents to Alter Resistance to Cytotoxic Anticancer Therapy
Cancer Res., December 1, 2007; 67(23): 11111 - 11116.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Ovcharenko, K. Kelnar, C. Johnson, N. Leng, and D. Brown
Genome-Scale MicroRNA and Small Interfering RNA Screens Identify Small RNA Modulators of TRAIL-Induced Apoptosis Pathway
Cancer Res., November 15, 2007; 67(22): 10782 - 10788.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. U. Mertens-Talcott, S. Chintharlapalli, X. Li, and S. Safe
The Oncogenic microRNA-27a Targets Genes That Regulate Specificity Protein Transcription Factors and the G2-M Checkpoint in MDA-MB-231 Breast Cancer Cells
Cancer Res., November 15, 2007; 67(22): 11001 - 11011.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. Lu, D. Katsaros, I. A. Rigault de la Longrais, O. Sochirca, and H. Yu
Hypermethylation of let-7a-3 in Epithelial Ovarian Cancer Is Associated with Low Insulin-like Growth Factor-II Expression and Favorable Prognosis
Cancer Res., November 1, 2007; 67(21): 10117 - 10122.
[Abstract] [Full Text] [PDF]

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 BloodHome page
J.-W. Cui, Y.-J. Li, A. Sarkar, J. Brown, Y.-H. Tan, M. Premyslova, C. Michaud, N. Iscove, G.-J. Wang, and Y. Ben-David
Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation
Blood, October 1, 2007; 110(7): 2631 - 2640.
[Abstract] [Full Text] [PDF]

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 J. Mol. Diagn.Home page
M. Kruhoffer, L. Dyrskjot, T. Voss, R. L.P. Lindberg, R. Wyrich, T. Thykjaer, and T. F. Orntoft
Isolation of Microarray-Grade Total RNA, MicroRNA, and DNA from a Single PAXgene Blood RNA Tube
J. Mol. Diagn., September 1, 2007; 9(4): 452 - 458.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
W. Zhang, J. E. Dahlberg, and W. Tam
MicroRNAs in Tumorigenesis: A Primer
Am. J. Pathol., September 1, 2007; 171(3): 728 - 738.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
C. D. Johnson, A. Esquela-Kerscher, G. Stefani, M. Byrom, K. Kelnar, D. Ovcharenko, M. Wilson, X. Wang, J. Shelton, J. Shingara, et al.
The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells
Cancer Res., August 15, 2007; 67(16): 7713 - 7722.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Galardi, N. Mercatelli, E. Giorda, S. Massalini, G. V. Frajese, S. A. Ciafre, and M. G. Farace
miR-221 and miR-222 Expression Affects the Proliferation Potential of Human Prostate Carcinoma Cell Lines by Targeting p27Kip1
J. Biol. Chem., August 10, 2007; 282(32): 23716 - 23724.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
Z. Yu, Z. Li, N. Jolicoeur, L. Zhang, Y. Fortin, E. Wang, M. Wu, and S.-H. Shen
Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers
Nucleic Acids Res., July 26, 2007; 35(13): 4535 - 4541.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Shell, S.-M. Park, A. R. Radjabi, R. Schickel, E. O. Kistner, D. A. Jewell, C. Feig, E. Lengyel, and M. E. Peter
Let-7 expression defines two differentiation stages of cancer
PNAS, July 3, 2007; 104(27): 11400 - 11405.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
W.-O. Lui, N. Pourmand, B. K. Patterson, and A. Fire
Patterns of Known and Novel Small RNAs in Human Cervical Cancer
Cancer Res., July 1, 2007; 67(13): 6031 - 6043.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
L. Gramantieri, M. Ferracin, F. Fornari, A. Veronese, S. Sabbioni, C.-G. Liu, G. A. Calin, C. Giovannini, E. Ferrazzi, G. L. Grazi, et al.
Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma
Cancer Res., July 1, 2007; 67(13): 6092 - 6099.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
K. P. Porkka, M. J. Pfeiffer, K. K. Waltering, R. L. Vessella, T. L.J. Tammela, and T. Visakorpi
MicroRNA Expression Profiling in Prostate Cancer
Cancer Res., July 1, 2007; 67(13): 6130 - 6135.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. Landais, S. Landry, P. Legault, and E. Rassart
Oncogenic Potential of the miR-106-363 Cluster and Its Implication in Human T-Cell Leukemia
Cancer Res., June 15, 2007; 67(12): 5699 - 5707.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
Y. M. Shah, K. Morimura, Q. Yang, T. Tanabe, M. Takagi, and F. J. Gonzalez
Peroxisome Proliferator-Activated Receptor {alpha} Regulates a MicroRNA-Mediated Signaling Cascade Responsible for Hepatocellular Proliferation
Mol. Cell. Biol., June 15, 2007; 27(12): 4238 - 4247.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
M. Negrini, M. Ferracin, S. Sabbioni, and C. M. Croce
MicroRNAs in human cancer: from research to therapy
J. Cell Sci., June 1, 2007; 120(11): 1833 - 1840.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Zhu, M.-L. Si, H. Wu, and Y.-Y. Mo
MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)
J. Biol. Chem., May 11, 2007; 282(19): 14328 - 14336.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
C. Sevignani, G. A. Calin, S. C. Nnadi, M. Shimizu, R. V. Davuluri, T. Hyslop, P. Demant, C. M. Croce, and L. D. Siracusa
MicroRNA genes are frequently located near mouse cancer susceptibility loci
PNAS, May 8, 2007; 104(19): 8017 - 8022.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
A. R.J. Young and M. Narita
Oncogenic HMGA2: short or small?
Genes & Dev., May 1, 2007; 21(9): 1005 - 1009.
[Full Text] [PDF]

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 Genes Dev.Home page
Y. S. Lee and A. Dutta
The tumor suppressor microRNA let-7 represses the HMGA2 oncogene
Genes & Dev., May 1, 2007; 21(9): 1025 - 1030.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
B. Zhou, S. Wang, C. Mayr, D. P. Bartel, and H. F. Lodish
miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely
PNAS, April 24, 2007; 104(17): 7080 - 7085.
[Abstract] [Full Text] [PDF]

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 aacredbookHome page
N. Yanaihara, M. Seike, A. Schetter, C.M. Croce, and C.C. Harris
MicroRNA Molecular Profiles in Cancer Diagnosis and Prognosis
Am. Assoc. Cancer Res. Educ. Book, April 14, 2007; 2007(1): 125 - 126.
[Full Text] [PDF]

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 J. Biol. Chem.Home page
F. Meng, R. Henson, H. Wehbe-Janek, H. Smith, Y. Ueno, and T. Patel
The MicroRNA let-7a Modulates Interleukin-6-dependent STAT-3 Survival Signaling in Malignant Human Cholangiocytes
J. Biol. Chem., March 16, 2007; 282(11): 8256 - 8264.
[Abstract] [Full Text] [PDF]

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 ScienceHome page
C. Mayr, M. T. Hemann, and D. P. Bartel
Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation
Science, March 16, 2007; 315(5818): 1576 - 1579.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
B. Brueckner, C. Stresemann, R. Kuner, C. Mund, T. Musch, M. Meister, H. Sultmann, and F. Lyko
The Human let-7a-3 Locus Contains an Epigenetically Regulated MicroRNA Gene with Oncogenic Function
Cancer Res., February 15, 2007; 67(4): 1419 - 1423.
[Abstract] [Full Text] [PDF]

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 BioinformaticsHome page
N. Yosef, Z. Yakhini, A. Tsalenko, V. Kristensen, A.-L. Borresen-Dale, E. Ruppin, and R. Sharan
A supervised approach for identifying discriminating genotype patterns and its application to breast cancer data
Bioinformatics, January 15, 2007; 23(2): e91 - e98.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
K. V. Prasanth and D. L. Spector
Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum
Genes & Dev., January 1, 2007; 21(1): 11 - 42.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
H. Osada and T. Takahashi
MicroRNAs in biological processes and carcinogenesis
Carcinogenesis, January 1, 2007; 28(1): 2 - 12.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
N. Sugito, H. Ishiguro, Y. Kuwabara, M. Kimura, A. Mitsui, H. Kurehara, T. Ando, R. Mori, N. Takashima, R. Ogawa, et al.
RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients
Clin. Cancer Res., December 15, 2006; 12(24): 7322 - 7328.
[Abstract] [Full Text] [PDF]


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