Abstract
MicroRNAs (miRNAs, miRs) play important roles in pathogenesis and development of human diseases, including malignancy. Some may affect tumor progression through targeting tumor suppressor genes. MiR-135b has been shown to be upregulated in CRC. In this study, we evaluated the role of miR-135b in colorectal cancer (CRC) and its regulatory role for metastasis suppressor-1 (MTSS1) and its mechanisms. The levels of miR-135b and MTSS1 gene expression in 35 CRC and corresponding cancer-adjacent tissues, 27 colorectal adenoma, and 16 normal tissue samples were quantified using qRT-PCR and western blot analysis. The effect of miR-135b on MTSS1 expression was assessed by miR-135b mimics or inhibitor transfection to deregulate miR-135b expression. The direct interaction between them was verified by 3′-UTR dual-luciferase reporter assay. Furthermore, the roles of miR-135b in regulating CRC cells migration and invasion properties were analyzed with miR-135b mimics or inhibitor-transfected cells and silenced expression of MTSS1 in miR-135b inhibitor transfected cells. CRC tissues showed significantly upregulated miR-135b expression and reduced MTSS1 expression. High miR-135b levels were significantly associated with lymph node and distant metastasis. The miR-135b inhibitor decreased miR-135b expression and caused MTSS1 upregulation at the post-transcriptional level. However, overexpression of miR-135b caused MTSS1 protein downregulation. The 3′-UTR of MTSS1 harbored a binding site for miR-135b. Finally, miR-135b inhibitor-transfected cells exhibited markedly reduced cell migration and invasive abilities, and this effect could be reversed by MTSS1-siRNA. Our results demonstrated that miR-135b downregulated MTSS1 expression and contributed to CRC cell invasion, indicating its involvement in CRC progression.
Similar content being viewed by others
References
Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N (2010) Colorectal cancer. Lancet 375:1030–1047
Schetter AJ, Okayama H, Harris CC (2012) The role of microRNAs in colorectal cancer. Cancer J 18(3):244–252
Xing Y, Qi J, Deng S, Wang C, Zhang L, Chen J (2013) Small interfering RNA targeting ILK inhibits metastasis in human tongue cancer cells through repression of epithelial-to-mesenchymal transition. Exp Cell Res 319(13):2058–2072
Qi P, Mi-die X, Ni S-j, Huang D, Wei P, Tan C, Zhou X-y, Xiang D (2013) Low expression of LOC285194 is associated with poor prognosis in colorectal cancer. J Trans Med 11:122
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9:775–789
Esquela-Kerscher A, Slack FJ (2006) Oncomirs–microRNAs with a role in cancer. Nat Rev Cancer 6:259–269
Osada H, Takahashi T (2007) MicroRNAs in biological processes and carcinogenesis. Carcinogenesis 28(1):2–12
Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, Yang RH, Feng Y, Wang FH, Tseng H-Y, Thorne RF, Jin L, Zhang XD (2013) MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer. Oncogene 32:1910–1920
Sarver AL, French AJ, Borralho PM, Thayanithy V, Oberg AL, Silverstein KA, Morlan BW, Riska SM, Boardman LA, Cunningham JM, Subramanian S, Wang L, Smyrk TC, Rodrigues CM, Thibodeau SN (2009) Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states. BMC Cancer 9:401
Xie F, Ye L, Chen J, Wu N, Zhang Z, Yang Y, Zhang L, Jiang WG (2011) The impact of metastasis suppressor-1, MTSS1, on oesophageal squamous cell carcinoma and its clinical significance. J Transl Med 9:95
Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112(4):453–465
Du P, Ye L, Li H, Yang Y, Jiang WG (2012) The tumour suppressive role of metastasis suppressor-1, MTSS1, in human kidney cancer, a possible connection with the SHH pathway. J Exp Ther Oncol 10(2):91–99
Du P, Ye L, Ruge F, Yang Y, Jiang WG (2011) Metastasis suppressor-1, MTSS1, acts as a putative tumor suppressor in human bladder cancer. Anticancer Res 31(10):3205–3212
Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60:167–179
Wu WK, Law PT, Lee CW, Cho CH, Fan D, Wu K, Yu J, Sung JJ (2011) MicroRNA in colorectal cancer: from benchtop to bedside. Carcinogenesis 32(3):247–253
Aslam MI, Patel M, Singh B, Jameson JS, Pringle JH (2012) MicroRNA manipulation in colorectal cancer cells: from laboratory to clinical application. J Transl Med 10:128
Lin CW, Chang YL, Chang YC, Lin JC, Chen CC, Pan SH, Wu CT, Chen HY, Yang SC, Hong TM, Yang PC (2013) MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Commun 4:1877
Arigoni M, Barutello G, Riccardo F, Ercole E, Cantarella D, Orso F, Conti L, Lanzardo S, Taverna D, Merighi I, Calogero RA, Cavallo F, Quaglino E (2013) miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2. Am J Pathol 182(6):2058–2070
Zhang L, Sun ZJ, Bian Y, Kulkarni AB (2013) MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett 331(2):230–238
Parr C, Jiang WG (2009) Metastasis suppressor 1 (MTSS1) demonstrates prognostic value and anti-metastatic properties in breast cancer. Eur J Cancer 45(9):1673–1683
Liu K, Wang G, Ding H, Chen Y, Yu G, Wang J (2010) Downregulation of metastasis suppressor 1 (MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer. BMC Cancer 10:428
Mustafa N, Martin TA, Jiang WG (2011) Metastasis tumour suppressor-1 and the aggressiveness of prostate cancer cells. Exp Ther Med 2(1):157–162
Zhou W, Li X, Liu F, Xiao Z, He M, Shen S, Liu S (2012) MiR-135a promotes growth and invasion of colorectal cancer via metastasis suppressor 1 in vitro. Acta Biochim Biophys Sin (Shanghai) 44(10):838–846
Author information
Authors and Affiliations
Corresponding authors
Additional information
Weiyun Wu and Zhuang Wang have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Wu, W., Wang, Z., Yang, P. et al. MicroRNA-135b regulates metastasis suppressor 1 expression and promotes migration and invasion in colorectal cancer. Mol Cell Biochem 388, 249–259 (2014). https://doi.org/10.1007/s11010-013-1916-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-013-1916-z