10 [82] A. Krtolica, S. Parrinello, S. Lockett, P. Y. Desprez, and J. Campisi, “Senescent ﬁbroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 21, pp. 12072–12077, 2001. [83] D. Bhaumik, G. K. Scott, S. Schokrpur et al., “MicroRNAs miR-146a/b negatively modulate the senescence-associated inﬂammatory mediators IL-6 and IL-8,” Aging, vol. 1, no. 4, pp. 402–411, 2009. [84] J. Kru¨tzfeldt, N. Rajewsky, R. Braich et al., “Silencing of microRNAs in vivo with ‘antagomirs’,” Nature, vol. 438, no. 7068, pp. 685–689, 2005. [85] J. Stenvang and S. Kauppinen, “MicroRNAs as targets for antisense-based therapeutics,” Expert Opinion on Biological Therapy, vol. 8, no. 1, pp. 59–81, 2008. [86] I. A. Asangani, S. A. K. Rasheed, D. A. Nikolova et al., “MicroRNA-21 (miR-21) post-transcriptionally downreg- ulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer,” Oncogene, vol. 27, no. 15, pp. 2128–2136, 2008. [87] L. B. Frankel, N. R. Christoﬀersen, A. Jacobsen, M. Lindow, A. Krogh, and A. H. Lund, “Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells,” The Journal of Biological Chemistry, vol. 283, no. 2, pp. 1026–1033, 2008. [88] Z. Lu, M. Liu, V. Stribinskis et al., “MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene,” Oncogene, vol. 27, no. 31, pp. 4373–4379, 2008. [89] S. Zhu, M. L. Si, H. Wu, and Y. Y. Mo, “MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1),” The Journal of Biological Chemistry, vol. 282, no. 19, pp. 14328– 14336, 2007. [90] F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob, and T. Patel, “MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer,” Gastroenterology, vol. 133, no. 2, pp. 647–658, 2007. [91] J. G. Zhang, J. J. Wang, F. Zhao, Q. Liu, K. Jiang, and G. H. Yang, “MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC),” Clinica Chimica Acta, vol. 411, no. 11- 12, pp. 846–852, 2010. [92] E. C. Connolly, K. van Doorslaer, L. E. Rogler, and C. E. Rogler, “Overexpression of miR-21 promotes an in vitro metastatic phenotype by targeting the tumor suppressor RHOB,” Molecular Cancer Research, vol. 8, no. 5, pp. 691– 700, 2010. [93] J. Zheng, H. Xue, T. Wang et al., “miR-21 downregulates the tumor suppressor P12CDK2AP1and stimulates cell prolifer- ation and invasion,” Journal of Cellular Biochemistry, vol. 112, no. 3, pp. 872–880, 2011. [94] M. L. Si, S. Zhu, H. Wu, Z. Lu, F. Wu, and Y. Y. Mo, “miR- 21-mediated tumor growth,” Oncogene, vol. 26, no. 19, pp. 2799–2803, 2007. [95] Y. Lu, J. Xiao, H. Lin et al., “A single anti-microRNA anti- sense oligodeoxyribonucleotide (AMO) targeting multiple microRNAs oﬀers an improved approach for microRNA interference,” Nucleic Acids Research, vol. 37, no. 3, article e24, 2009. [96] M. S. Ebert, J. R. Neilson, and P. A. Sharp, “MicroRNA sponges: competitive inhibitors of small RNAs in mam- malian cells,” Nature Methods, vol. 4, no. 9, pp. 721–726, 2007. Journal of Aging Research [97] C. M. Loya, C. S. Lu, D. Van Vactor, and T. A. Fulga, “Trans- genic microRNA inhibition with spatiotemporal speciﬁcity in intact organisms,” Nature Methods, vol. 6, no. 12, pp. 897– 903, 2009. [98] J. Xiao, B. Yang, H. Lin, Y. Lu, X. Luo, and Z. Wang, “Novel approaches for gene-speciﬁc interference via manipulating actions of microRNAs: examination on the pacemaker chan- nel genes HCN2 and HCN4,” Journal of Cellular Physiology, vol. 212, no. 2, pp. 285–292, 2007. [99] Y. Akao, Y. Nakagawa, and T. Naoe, “let-7 microRNA functions as a potential growth suppressor in human colon cancer cells,” Biological and Pharmaceutical Bulletin, vol. 29, no. 5, pp. 903–906, 2006. [100] Y. Xiong, J. H. Fang, J. P. Yun et al., “Eﬀects of microrna- 29 on apoptosis, tumorigenicity, and prognosis of hepato- cellular carcinoma,” Hepatology, vol. 51, no. 3, pp. 836–845, 2010. [101] S. M. Johnson, H. Grosshans, J. Shingara et al., “RAS is regulated by the let-7 microRNA family,” Cell, vol. 120, no. 5, pp. 635–647, 2005. [102] C. Mayr, M. T. Hemann, and D. P. Bartel, “Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation,” Science, vol. 315, no. 5818, pp. 1576–1579, 2007. [103] D. W. M u¨ller and A. K. Bosserhoﬀ, “Integrin β expression is regulated by let-7a miRNA in malignant melanoma,” Oncogene, vol. 27, no. 52, pp. 6698–6706, 2008. [104] J. Schultz, P. Lorenz, G. Gross, S. Ibrahim, and M. Kunz, “MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage- independent growth,” Cell Research, vol. 18, no. 5, pp. 549– 557, 2008. [105] S. Shimizu, T. Takehara, H. Hikita et al., “The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carci- noma,” Journal of Hepatology, vol. 52, no. 5, pp. 698–704, 2010. [106] T. S. Wong, O. Y. Man, C. M. Tsang et al., “MicroRNA let- 7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression,” Journal of Can- cer Research and Clinical Oncology, vol. 137, no. 3, pp. 415– 422, 2011. [107] A. Esquela-Kerscher, P. Trang, J. F. Wiggins et al., “The let-7 microRNA reduces tumor growth in mouse models of lung cancer,” Cell Cycle, vol. 7, no. 6, pp. 759–764, 2008. [108] M. S. Kumar, S. J. Erkeland, R. E. Pester et al., “Suppression of non-small cell lung tumor development by the let-7 microRNA family,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 10, pp. 3903–3908, 2008. [109] P. Trang, P. P. Medina, J. F. Wiggins et al., “Regression of murine lung tumors by the let-7 microRNA,” Oncogene, vol. 29, no. 11, pp. 1580–1587, 2010. [110] F. F. Lan, H. Wang, Y. C. Chen et al., “Hsa-let-7g inhibits pro- liferation of hepatocellular carcinoma cells by downregula- tion of c-Myc and upregulation of p16INK4A,” International Journal of Cancer, vol. 128, no. 2, pp. 319–331, 2011. [111] J. F. Wiggins, L. Ruﬃno, K. Kelnar et al., “Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34,” Cancer Research, vol. 70, no. 14, pp. 5923– 5930, 2010. [112] F. Sun, H. Fu, Q. Liu et al., “Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest,” FEBS Letters, vol. 582, no. 10, pp. 1564–1568, 2008.