p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB

Zhang,Quan; Cao,Li-Ye; Cheng,Shu-Jie; Zhang,Ai-Min; Jin,Xiao-Shi; Li,Yong

doi:10.3892/or.2015.3715

p53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB

Authors:
- Quan Zhang
- Li-Ye Cao
- Shu-Jie Cheng
- Ai-Min Zhang
- Xiao-Shi Jin
- Yong Li
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Affiliations: Department of Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China, Department of Ultrasound, The Affiliated Hospital of Hebei University, Baoding, Hebei, P.R. China, Department of Surgery, The Affiliated Hospital of Hebei University, Baoding, Hebei, P.R. China
Published online on: January 14, 2015 https://doi.org/10.3892/or.2015.3715
Pages: 1335-1341

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Abstract

In recent years, miR-1246 has been identified as a transcriptional target of p53 in Down syndrome and may provide a new p53-miR-1246-DYRK1A-NFAT pathway in cancer. The present study aimed to explore the role of miR-1246 in the tumorigenesis of human hepatocellular carcinoma (HCC). We found that wild-type p53 regulated the expression of miR-1246 in HCC cell lines, and alteration of miR-1246 modulated cell proliferation, colony formation ability and apoptosis. The nuclear factor I/B (NFIB), an oncogene, was identified as a direct target gene of miR-1246 using a fluorescent reporter assay. Overexpression of NFIB abolished the regulation of cell apoptosis caused by miR-1246 in HepG2 cells. This finding suggests that miR-1246 is regulated by p53 and suppresses the growth of human HCC by targeting NFIB. Here, we propose a new p53-miR-1246-NFIB pathway in HCC.

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1	Collavin L, Lunardi A and Del Sal G: p53-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ. 17:901–911. 2010. View Article : Google Scholar : PubMed/NCBI
2	Qian Y and Chen X: Tumor suppression by p53: making cells senescent. Histol Histopathol. 25:515–526. 2010.PubMed/NCBI
3	Menendez D, Inga A and Resnick MA: The expanding universe of p53 targets. Nat Rev Cancer. 9:724–737. 2009. View Article : Google Scholar : PubMed/NCBI
4	Hermeking H: The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–199. 2010. View Article : Google Scholar
5	Hermeking H: MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer. 12:613–626. 2012. View Article : Google Scholar : PubMed/NCBI
6	Shin S, Cha HJ, Lee EM, et al: MicroRNAs are significantly influenced by p53 and radiation in HCT116 human colon carcinoma cells. Int J Oncol. 34:1645–1652. 2009.PubMed/NCBI
7	He L, He X, Lowe SW and Hannon GJ: microRNAs join the p53 network - another piece in the tumour-suppression puzzle. Nat Rev Cancer. 7:819–822. 2007. View Article : Google Scholar : PubMed/NCBI
8	Feng Z, Zhang C, Wu R and Hu W: Tumor suppressor p53 meets microRNAs. J Mol Cell Biol. 3:44–50. 2011. View Article : Google Scholar : PubMed/NCBI
9	Zhang W and Cohen SM: The Hippo pathway acts via p53 and microRNAs to control proliferation and proapoptotic gene expression during tissue growth. Biol Open. 2:822–828. 2013. View Article : Google Scholar : PubMed/NCBI
10	Liao JM, Cao B, Zhou X and Lu H: New insights into p53 functions through its target microRNAs. J Mol Cell Biol. 6:206–213. 2014. View Article : Google Scholar : PubMed/NCBI
11	Tarasov V, Jung P, Verdoodt B, et al: Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 6:1586–1593. 2007. View Article : Google Scholar : PubMed/NCBI
12	Chang TC, Wentzel EA, Kent OA, et al: Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 26:745–752. 2007. View Article : Google Scholar : PubMed/NCBI
13	Raver-Shapira N, Marciano E, Meiri E, et al: Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 26:731–743. 2007. View Article : Google Scholar : PubMed/NCBI
14	Bommer GT, Gerin I, Feng Y, et al: p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 17:1298–1307. 2007. View Article : Google Scholar : PubMed/NCBI
15	Corney DC, Flesken-Nikitin A, Godwin AK, Wang W and Nikitin AY: MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433–8438. 2007. View Article : Google Scholar : PubMed/NCBI
16	He L, He X, Lim LP, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI
17	Liao JM, Zhou X, Zhang Y and Lu H: miR-1246: a new link of the p53 family with cancer and Down syndrome. Cell Cycle. 11:2624–2630. 2012. View Article : Google Scholar : PubMed/NCBI
18	Zhang Y, Liao JM, Zeng SX and Lu H: p53 downregulates Down syndrome-associated DYRK1A through miR-1246. EMBO Rep. 12:811–817. 2011. View Article : Google Scholar : PubMed/NCBI
19	Li W, Wu YF, Xu RH, Lu H, Hu C and Qian H: miR-1246 releases RTKN2-dependent resistance to UVB-induced apoptosis in HaCaT cells. Mol Cell Biochem. 394:299–306. 2014. View Article : Google Scholar : PubMed/NCBI
20	Chen J, Yao D, Zhao S, et al: MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2. Arch Gynecol Obstet. 290:725–732. 2014. View Article : Google Scholar : PubMed/NCBI
21	Xu LJ, Jiang T, Zhao W, et al: Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression. PLoS One. 9:e952722014. View Article : Google Scholar : PubMed/NCBI
22	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar
23	Huang S and He X: The role of microRNAs in liver cancer progression. Br J Cancer. 104:235–240. 2011. View Article : Google Scholar :
24	Wu N, Liu X, Xu X, et al: MicroRNA-373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma. FEBS J. 278:2044–2054. 2011. View Article : Google Scholar : PubMed/NCBI
25	Zhou L, Yang ZX, Song WJ, et al: MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma. Int J Oncol. 43:661–669. 2013.PubMed/NCBI
26	Zhou J, Lu S, Yang S, et al: MicroRNA-127 post-transcriptionally downregulates Sept7 and suppresses cell growth in hepatocellular carcinoma cells. Cell Physiol Biochem. 33:1537–1546. 2014. View Article : Google Scholar : PubMed/NCBI
27	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
28	Ma L, Young J, Prabhala H, et al: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 12:247–256. 2010.PubMed/NCBI
29	Tang H, Yao L, Tao X, et al: miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1. Int J Mol Med. 32:381–388. 2013.PubMed/NCBI
30	Dooley AL, Winslow MM, Chiang DY, et al: Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. 25:1470–1475. 2011. View Article : Google Scholar : PubMed/NCBI
31	Moon HG, Hwang KT, Kim JA, et al: NFIB is a potential target for estrogen receptor-negative breast cancers. Mol Oncol. 5:538–544. 2011. View Article : Google Scholar : PubMed/NCBI