Differential Expression Profile Analysis of MicroRNAs in Doxorubicin-induced Hepatoma Cell Line HepG2

doi:10.13560/j.cnki.biotech.bull.1985.2016.06.036

Abstract

Abstract: The aims of this work are to study the miRNAs of hepatoma cell HepG2 involving in the response to doxorubicin-induced DNA damages，and to analyze the these miRNAs target genes and the biological processes and pathways related to the response to the hepatoma DNA damages. Small RNA sequencing was used to detect the differentially expressed miRNAs between doxorubicin-treated hepatocellular carcinoma cell line HepG2 and untreated one，and the functions of target genes were analyzed by GO(gene ontology)and KEGG pathway enrichment. Remarkably，68 significantly differentially-expressed miRNAs were identified，13 miRNAs were up-regulated and 55 were down-regulated. After the functional analysis of miRNA targets，the 53 miRNAs were enriched in the biological processes of cell proliferation，cell apoptosis，cell invasion and cell cycle arrest，as well as the pathways of p53 signal，cancer，Wnt signal and MPK，etc. The results demonstrate that these differentially-expressed miRNAs are correlated with DNA damage response-related biological processes and signaling pathways，indicating the prominent importance of these miRNAs in the doxorubicin-induced DNA damage response in hepatocellular carcinoma.

Key words: doxorubicin, hepatocellular carcinoma, DNA damage, small RNA sequencing, microRNAs

YANG Ya-lan, GUO Zhi-yun, DING Ruo-fan, MAO Can-quan, GUO Jian-xiu, XIONG Li-li. Differential Expression Profile Analysis of MicroRNAs in Doxorubicin-induced Hepatoma Cell Line HepG2[J]. Biotechnology Bulletin, 2016, 32(6): 244-249.

References

[1]Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma：A comprehensive review[J]. World J Hepatol, 2015, 7(26)：2648-2663.
[2]Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2)：87-108.
[3]Bartel DP. MicroRNAs：target recognition and regulatory functions[J]. Cell, 2009, 136(2)：215-233.
[4]Wouters MD, van Gent DC, et al. MicroRNAs, the DNA damage response and cancer[J]. Mutat Res, 2011, 717(1-2)：54-66.
[5]Hu H, Gatti RA. MicroRNAs：new players in the DNA damage response[J]. J Mol Cell Biol, 2011, 3(3)：151-158.
[6]Di Francesco A, De Pitta C, Moret F, et al. The DNA-damage response to gamma-radiation is affected by miR-27a in A549 Cells[J]. Int J Mol Sci, 2013, 14(9)：17881-17896.
[7]Agarwal V, Bell GW, Nam JW, et al. Predicting effective microRNA target sites in mammalian mRNAs[J]. Elife, 2015, 4. doi：10.7554/elife.05005.
[8]Betel D, Koppal A, Agius P, et al. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites[J]. Genome Biol, 2010, 11(8)：R90.
[9]Wong N, Wang X. MiRDB：an online resource for microRNA target prediction and functional annotations[J]. Nucleic Acids Res, 2015, 43：D146-D152.
[10]Vlachos IS, Paraskevopoulou MD, Karagkouni D, et al. DIANA-TarBase v7. 0：indexing more than half a million experimentally supported miRNA：mRNA interactions[J]. Nucleic Acids Res, 2015, 43：D153-D159.
[11]Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J]. Nat Protoc, 2009, 4(1)：44-57.
[12]Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools：paths toward the comprehensive functional analysis of large gene lists[J]. Nucleic Acids Res, 2009, 37(1)：1-13.
[13]Wang Y, Taniguchi T. MicroRNAs and DNA damage response：implications for cancer therapy[J]. Cell Cycle, 2013, 12(1)：32-42.
[14]Wan G, Mathur R, Hu X, et al. miRNA response to DNA damage[J]. Trends Biochem Sci, 2011, 36(9)：478-484.
[15]Huang H, Zhu Y, Li S. MicroRNA-122 mimic transfection contributes to apoptosis in HepG2 cells[J]. Mol Med Rep, 2015, 12(5)：6918-6924.
[16]Xu Q, Zhang M, et al. MicroRNA-122 affects cell aggressiveness and apoptosis by targeting PKM2 in human hepatocellular carcinoma[J]. Oncol Rep, 2015, 34(4)：2054-2064.
[17]Li D, Yang P, Li H, et al. MicroRNA-1 inhibits proliferation of hepatocarcinoma cells by targeting endothelin-1[J]. Life Sci, 2012, 91(11-12)：440-447.
[18]Yang H, Lan P, Hou Z, et al. Histone deacetylase inhibitor SAHA epigenetically regulates miR-17-92 cluster and MCM7 to upregulate MICA expression in hepatoma[J]. Br J Cancer, 2015, 112(1)：112-121.
[19]Yan HL, Xue G, Mei Q, et al. Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis[J]. Embo J, 2009, 28(8)：2719-2732.
[20]Zhu H, Han C, Wu T. MiR-17-92 cluster promotes hepatocarcinogenesis[J]. Carcinogenesis, 2015, 36(10)：1213-1222.