Abstract
MicroRNAs (miRNAs) play essential roles in the progression of hepatocellular carcinoma (HCC). miR-144 acts as a tumor suppressor in some malignancies, while its role in HCC is unclear. Here, we found that miR-144 was significantly decreased in HCC tissues and cell lines. Forced overexpression of miR-144 remarkably reduced cell proliferation, increased apoptosis, and suppressed migration and invasion of HCC cells. E2F transcription factor 3 (E2F3) was identified as a target of miR-144 in HCC cells. Moreover, E2F3 overexpression partially attenuated the tumor suppressive effects of miR-144, and the expression of E2F3 was negatively correlated with miR-144 level in HCC tissues. Our data suggest that miR-144 might suppress the growth and motility of HCC cells partially by targeting E2F3.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Perez-Saborido B, de los Galanes SJ, Meneu-Diaz JC, Romero CJ, Elola-Olaso AM, Suarez YF, et al. Tumor recurrence after liver transplantation for hepatocellular carcinoma: recurrence pathway and prognostic factors. Transplant Proc. 2007;39:2304–7.
Singal AG, Nehra M, Adams-Huet B, Yopp AC, Tiro JA, Marrero JA, et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol. 2013;108:425–32.
Liu AM, Xu Z, Shek FH, Wong KF, Lee NP, Poon RT, et al. Mir-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma. PLoS One. 2014;9:e86872.
Huang XY, Yao JG, Huang HD, Wang C, Ma Y, Xia Q, et al. MicroRNA-429 modulates hepatocellular carcinoma prognosis and tumorigenesis. Gastroenterol Res Pract. 2013;2013:804128.
Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19:232–43.
Zhou J, Tao Y, Peng C, Gu P, Wang W. Mir-503 regulates metastatic function through Rho guanine nucleotide exchanger factor 19 in hepatocellular carcinoma. J Surg Res. 2013
Xu T, Zhu Y, Xiong Y, Ge YY, Yun JP, Zhuang SM. MicroRNA-195 suppresses tumorigenicity and regulates G1/S transition of human hepatocellular carcinoma cells. Hepatology. 2009;50:113–21.
Iwaya T, Yokobori T, Nishida N, Kogo R, Sudo T, Tanaka F, et al. Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway. Carcinogenesis. 2012;33:2391–7.
Zha W, Cao L, Shen Y, Huang M. Roles of Mir-144-ZFX pathway in growth regulation of non-small-cell lung cancer. PLoS One. 2013;8:e74175.
Namlos HM, Meza-Zepeda LA, Baroy T, Ostensen IH, Kresse SH, Kuijjer ML, et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 2012;7:e48086.
Katayama Y, Maeda M, Miyaguchi K, Nemoto S, Yasen M, Tanaka S, et al. Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling. Oncol Lett. 2012;4:817–23.
Milazzo M, Fornari F, Gramantieri L. MicroRNA and hepatocellular carcinoma: biology and prognostic significance. Minerva Gastroenterol Dietol. 2011;57:257–71.
Akiyoshi S, Fukagawa T, Ueo H, Ishibashi M, Takahashi Y, Fabbri M, et al. Clinical significance of miR-144-ZFX axis in disseminated tumour cells in bone marrow in gastric cancer cases. Br J Cancer. 2012;107:1345–53.
Sureban SM, May R, Lightfoot SA, Hoskins AB, Lerner M, Brackett DJ, et al. DCAMKL-1 regulates epithelial-mesenchymal transition in human pancreatic cells through a miR-200a-dependent mechanism. Cancer Res. 2011;71:2328–38.
Zhang LY, Ho-Fun Lee V, Wong AM, Kwong DL, Zhu YH, Dong SS, et al. MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. Carcinogenesis. 2013;34:454–63.
Xiao F, Zhang W, Chen L, Chen F, Xie H, Xing C, et al. MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma. J Transl Med. 2013;11:195.
Foster CS, Falconer A, Dodson AR, Norman AR, Dennis N, Fletcher A, et al. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene. 2004;23:5871–9.
Feber A, Clark J, Goodwin G, Dodson AR, Smith PH, Fletcher A, et al. Amplification and overexpression of E2F3 in human bladder cancer. Oncogene. 2004;23:1627–30.
Vimala K, Sundarraj S, Sujitha MV, Kannan S. Curtailing overexpression of E2F3 in breast cancer using siRNA (E2F3)-based gene silencing. Arch Med Res. 2012;43:415–22.
Huang L, Luo J, Cai Q, Pan Q, Zeng H, Guo Z, et al. MicroRNA-125b suppresses the development of bladder cancer by targeting E2F3. Int J Cancer J Int Cancer. 2011;128:1758–69.
Zhang QQ, Xu H, Huang MB, Ma LM, Huang QJ, Yao Q, et al. MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. Neuro Oncol. 2012;14:278–87.
Zeng X, Yin F, Liu X, Xu J, Xu Y, Huang J, et al. Upregulation of E2F transcription factor 3 is associated with poor prognosis in hepatocellular carcinoma. Oncol Rep. 2014;31:1139–46.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cao, T., Li, H., Hu, Y. et al. miR-144 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting E2F3. Tumor Biol. 35, 10759–10764 (2014). https://doi.org/10.1007/s13277-014-2017-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-014-2017-7