Abstract
Dysregulation of microRNA-100 (miR-100) has been shown to be involved in cancer tumorigenesis and progression of several cancer types. However, its expression patterns in tumors are controversial. The aim of this study was to investigate the expression and clinical significance of miR-100 in colorectal cancer (CRC). Quantitative real-time PCR was used to analyze the expression of miR-100 in 138 pairs of human CRC and adjacent normal tissues. The prognostic values of miR-100 in CRC were also analyzed. The results showed that the miR-100 expression was significantly downregulated in CRC tissues when compared to adjacent normal tissues (P < 0.001). Also, low miR-100 expression was observed to be significantly correlated with larger tumor size (P = 0.023), higher incidence of lymph node metastasis (P = 0.009), and advanced TNM stage (P = 0.016). More importantly, Kaplan–Meier analysis showed that CRC patients with low miR-100 expression tended to have shorter overall survival. In multivariate analysis stratified for known prognostic variables, low miR-100 expression was identified as an independent prognostic factor for overall survival. In conclusion, our data indicated for the first time that the downregulation of miR-100 was associated with advanced clinical features and poor prognosis of CRC patients, suggesting that miR-100 downregulation may serve as an unfavorable prognostic biomarker in CRC.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30. doi:10.3322/caac.21166.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.
He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522–31. doi:10.1038/nrg1379.
Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302(1):1–12. doi:10.1016/j.ydbio.2006.08.028.
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8. doi:10.1038/nature03702.
Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9(10):775–89. doi:10.1038/nrd3179.
Zhou XJ, Dong ZG, Yang YM, Du LT, Zhang X, Wang CX. Limited diagnostic value of microRNAs for detecting colorectal cancer: a meta-analysis. Asian Pac J Cancer Prev. 2013;14(8):4699–704.
Nair VS, Maeda LS, Ioannidis JP. Clinical outcome prediction by microRNAs in human cancer: a systematic review. J Natl Cancer Inst. 2012;104(7):528–40. doi:10.1093/jnci/djs027.
Ma XL, Liu L, Liu XX, Li Y, Deng L, Xiao ZL, et al. Prognostic role of microRNA-21 in non-small cell lung cancer: a meta-analysis. Asian Pac J Cancer Prev. 2012;13(5):2329–34.
Shi W, Alajez NM, Bastianutto C, Hui AB, Mocanu JD, Ito E, et al. Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer. Int J Cancer. 2010;126(9):2036–48. doi:10.1002/ijc.24880.
Oliveira JC, Brassesco MS, Morales AG, Pezuk JA, Fedatto PF, da Silva GN, et al. MicroRNA-100 acts as a tumor suppressor in human bladder carcinoma 5637 cells. Asian Pac J Cancer Prev. 2011;12(11):3001–4.
Peng DX, Luo M, Qiu LW, He YL, Wang XF. Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer. Oncol Rep. 2012;27(4):1238–44. doi:10.3892/or.2012.1625.
Cairo S, Wang Y, de Reynies A, Duroure K, Dahan J, Redon MJ, et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc Natl Acad Sci USA. 2010;107(47):20471–6. doi:10.1073/pnas.1009009107.
Wang G, Chen L, Meng J, Chen M, Zhuang L, Zhang L. Overexpression of microRNA-100 predicts an unfavorable prognosis in renal cell carcinoma. Int Urol Nephrol. 2013;45(2):373–9. doi:10.1007/s11255-012-0374-y.
Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92. doi:10.1038/onc.2011.208.
Peng H, Luo J, Hao H, Hu J, Xie SK, Ren D, et al. MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B. Oncol Rep. 2014;31(5):2055–62. doi:10.3892/or.2014.3075.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8. doi:10.1006/meth.2001.1262.
Woolf SH. The best screening test for colorectal cancer—a personal choice. N Engl J Med. 2000;343(22):1641–3. doi:10.1056/nejm200011303432211.
Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal cancer. Lancet. 2005;365(9454):153–65. doi:10.1016/s0140-6736(05)17706-x.
Perera RJ, Ray A. MicroRNAs in the search for understanding human diseases. BioDrugs. 2007;21(2):97–104.
Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008;27(15):2128–36. doi:10.1038/sj.onc.1210856.
Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299(4):425–36. doi:10.1001/jama.299.4.425.
Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, et al. miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res. 2012;72(14):3631–41. doi:10.1158/0008-5472.can-12-0667.
Feng B, Dong TT, Wang LL, Zhou HM, Zhao HC, Dong F, et al. Colorectal cancer migration and invasion initiated by microRNA-106a. PloS One. 2012;7(8):e43452. doi:10.1371/journal.pone.0043452.
Zhang Y, Wang Z, Chen M, Peng L, Wang X, Ma Q, et al. MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer. Mol Cancer. 2012;11:23. doi:10.1186/1476-4598-11-23.
Zeng Y, Qu X, Li H, Huang S, Wang S, Xu Q, et al. MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2. FEBS Lett. 2012;586(16):2375–81. doi:10.1016/j.febslet.2012.05.049.
Huang L, Lin JX, Yu YH, Zhang MY, Wang HY, Zheng M. Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix. PloS One. 2012;7(3):e33762. doi:10.1371/journal.pone.0033762.
Henson BJ, Bhattacharjee S, O’Dee DM, Feingold E, Gollin SM. Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosomes Cancer. 2009;48(7):569–82. doi:10.1002/gcc.20666.
Doghman M, El Wakil A, Cardinaud B, Thomas E, Wang J, Zhao W, et al. Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors. Cancer Res. 2010;70(11):4666–75. doi:10.1158/0008-5472.can-09-3970.
Leite KR, Tomiyama A, Reis ST, Sousa-Canavez JM, Sanudo A, Camara-Lopes LH, et al. MicroRNA expression profiles in the progression of prostate cancer–from high-grade prostate intraepithelial neoplasia to metastasis. Urol Oncol. 2013;31(6):796–801. doi:10.1016/j.urolonc.2011.07.002.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, P., Xi, Q., Wang, Q. et al. Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in colorectal cancer. Med Oncol 31, 235 (2014). https://doi.org/10.1007/s12032-014-0235-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-014-0235-x