Hsa-miR-125b在人胃癌耐药细胞株中的表达及其靶基因的功能分析

doi:10.3724/SP.J.1005.2014.0119

[an error occurred while processing this directive]

Hereditas(Beijing) ›› 2014, Vol. 36 ›› Issue (2): 119-126.doi: 10.3724/SP.J.1005.2014.0119

Previous Articles Next Articles

Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer

Yan Cheng^1,2, Lin Chen³, Xin Cao², Siqimeige Ha², Xiaodong Xie¹

1. Institute of Genetics, School of Basic Medical Science, Lanzhou University, Lanzhou 730000, China;
2. Experimental Center, Northwest University for Nationalities, Lanzhou 730030, China;
3. Department of Infectious Diseases, First Affiliated Hospital of Lanzhou University, Lanzhou 730000, China

Received:2013-07-17 Revised:2013-10-31 Online:2014-02-20 Published:2014-01-25

Abstract

Abstract:

The expression of hsa-miR-125b is significantly downregulated in the fluorouracil-resistant cell line of human gastric cancer (BGC823/Fu). In order to investigate the role of hsa-miR-125b in the drug-resistance acquisition process of human gastric cancer, we performed a series of analysis on the sequence characteristics, species conservation, target genes, function annotation and signal transduction pathway enrichment of hsa-miR-125b using a combined bioinformatic approach such as miRbase, TargetScan6.2, PicTar, miRanda, Gene Ontology(GO) and KEGG. The results showed that the sequence of miR-125b is highly conserved in multiple species. A total of 79 target genes related to transcription regulation, protein binding, enzyme activity (P<0.001) were predicted by bioinformatics software. These genes involved in many biological processes including cell cycle, cell proliferation, cell apoptosis and cell responses to cytokine, drug responses and DNA damage (P<0.001). And these target genes mainly belong to MAPK, Wnt and p53 signal transduction pathways (P<0.01). The results revealed that hsa-miR-125b may regulate multiple biological processes and signal transduction pathways, and drug-resistant occurrence is associated with cell proliferation, cell apoptosis, cell cycle and signaling pathways including MAPK, Wnt and p53. We suggest that hsa-miR-125b may affect chemosensitivity by regulating target genes involved in the above processes and these target genes might be reliable candidates for exploring the role of hsa-miR-125b in tumor chemoresistance.

Key words: hsa-miR-125b, bioinformatics, target gene, chemotherapy resistance, human gastric cancer

Yan Cheng, Lin Chen, Xin Cao, Siqimeige Ha, Xiaodong Xie. Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer[J]. Hereditas(Beijing), 2014, 36(2): 119-126.

References

[1] Lippert TH, Ruoff HJ, Volm M. Intrinsic and acquired drug resistance in malignant tumors. The main reason for therapeutic failure. Arzneimittelforschung, 2008, 58(6): 261–264. <\p>

[2] O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. C-Myc-regulated microRNAs modulate E2F1 expres-sion. Nature, 2005, 435(7043): 839–843. <\p>

[3] Blower PE, Chung JH, Verducci JS, Lin S, Park JK, Dai Z, Liu CG, Schmittgen TD, Reinhold WC, Croce CM, Weinstein JN, Sadee W. MiRNAs modulate the chemosen-sitivity of tumor cells. Mol Cancer Ther, 2008, 7(1): 1–9. <\p>

[4] Zheng T, Wang J, Chen X, Liu L. Role of microRNA in anti-cancer drug resistance. Int J Cancer, 2010, 126(1): 2–10. <\p>

[5] Iorio MV, Croce CM. MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol, 2009, 27(34): 5848–5856. <\p>

[6] Kozomara A, Griffiths-Jones S. miRBase: integrating mi-croRNA annotation and deep-sequencing data. Nucleic Acids Res, 2011, 39: 152–157. <\p>

[7] Lewis B P, Burge C B, Bartel V. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are MicroRNA targets. Cell, 2005, 120(1): 15–20. <\p>

[8] Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA. org resource: targets and expression. Nucleic Acids Res, 2008, 36: 149–153. <\p>

[9] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL, Tsai WT, Chen GZ, Lee CJ, Chiu CM, Chien CH, Wu MC, Huang CY, Tsou AP, Huang HD. miRTarBase: a database curates experimentally validated microRNA-target inter-actions. Nucleic Acids Research, 2011, 39: 163–169. <\p>

[10] Fojo T. Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoterregions, epigenetic changes and microRNAs. Drug Resist Updat, 2007, 10(1–2): 59–67. <\p>

[11] Sun YM, Lin KY, Chen YQ. Diverse functions of miR-125 family in differentcell contexts. J Hematol Oncol, 2013, 6: 6. <\p>

[12] Xia HF, He TZ, Liu CM, Cui Y, Song PP, Jin XH, Ma X. MiR-125b expression affects the proliferation and apop-tosis of human glioma cells by targeting Bmf. Cell Physiol Biochem, 2009, 23(4–6): 347–358. <\p>

[13] Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y. miR- 125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun, 2008, 368(2): 267–272. <\p>

[14] 胡斌, 吴爱国, 李学孝, 纪术峰, 王梦川, 吴凯, 邵国利. miR-125b-1 增强乳腺癌SKBR-3 细胞对紫杉醇的药物敏感性. 热带医学杂志, 2012, 12(7): 789–792. <\p>

[15] 智慧, 朱伟, 王同杉, 王建, 束永前, 刘平. miR-125b靶向抑制BCL2、MCL1表达对胃癌SGC7901/VCR细胞多药耐药性的影响. 南京医科大学学报, 2011, 6: 777–781. <\p>

[16] Kong F, Sun C, Wang Z, Han L, Weng D, Lu Y, Chen G. miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1(BAK1)expression. J Huazhong Univ Sci Technolog Med Sci, 2011, 31(4): 543–549. <\p>

[17] Shi L, Zhang J, Pan T, Zhou J, Gong W, Liu N, Fu Z, You Y. MiR-125b is critical for the suppression of human U251 glioma stem cell proliferation. Brain Res, 2010, 1312: 120–126. <\p>

[18] Duman BB, Sahin B, Acikalin A, Ergin M, Zorludemir S. PTEN, Akt, MAPK, p53 and p95 expression to predict trastuzumab resistance in HER2 positive breast cancer. J BUON, 2013, 18(1): 44–50. <\p>

[19] Pritchard AL, Hayward NK. Molecular pathways: mito-gen-activated protein kinase pathway mutations and drug resistance. Clin Cancer Res, 2013, 19(9): 2301– 2309. <\p>

[20] Paunovic V, Harnett MM. Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis. Drugs, 2013, 73(2): 101–115.

Metrics

Comments

www.chinagene.cn
备案号：京ICP备09063187号

Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Shanshan Wang, Wanyi Zhao, Huixiao Wu, Meng Shu, Jiaxin Yuan, Li Fang, Chao Xu. Research on the variants of FGFR1 and CEP290 genes in idiopathic hypogonadotropin hypogonadism [J]. Hereditas(Beijing), 2022, 44(10): 937-949.
[2]	Hong Xiang, Xiaohu Yang, Liangxia Ai, Yanping Pan, Yong Hu. Bioinformatics analysis of differentially expressed genes on alopecia [J]. Hereditas(Beijing), 2020, 42(2): 172-182.
[3]	Hongqiang Lyu, Lele Hao, Erhu Liu, Zhifang Wu, Jiuqiang Han, Yuan Liu. Current status and future perspectives in bioinformatical analysis of Hi-C data [J]. Hereditas(Beijing), 2020, 42(1): 87-99.
[4]	Chao He,Wenlong Shen,Ping Li,Yan Zhang,Jing Zeng,Zuoming Yin,Zhihu Zhao. Bioinformatics analysis of Alu components at the level of genome 3D structure [J]. Hereditas(Beijing), 2019, 41(3): 254-261.
[5]	Ziying Huang, Long Li, Qianqian Li, Xiangdong Liu, Changchun Li. The effect of lncRNA TCONS_00815878 on differentiation of porcine skeletal muscle satellite cells [J]. Hereditas(Beijing), 2019, 41(12): 1119-1128.
[6]	Yuansheng Zhang,Lin Xia,Jian Sang,Man Li,Lin Liu,Mengwei Li,Guangyi Niu,Jiabao Cao,Xufei Teng,Qing Zhou,Zhang Zhang. The BIG Data Center’s database resources [J]. Hereditas(Beijing), 2018, 40(11): 1039-1043.
[7]	Xiaohua Xiang, Xinru Wu, Jiangtao Chao, Minglei Yang, Fan Yang, Guo Chen, Guanshan Liu, Yuanying Wang. Genome-wide identification and expression analysis of the WRKY gene family in common tobacco (Nicotiana tabacum L.) [J]. Hereditas(Beijing), 2016, 38(9): 840-856.
[8]	Xiaoxu Li, Cheng Liu, Wei Li, Zenglin Zhang, Xiaoming Gao, Hui Zhou, Yongfeng Guo. Genome-wide identification, phylogenetic analysis and expression profiling of the WOX family genes in Solanum lycopersicum [J]. HEREDITAS(Beijing), 2016, 38(5): 444-460.
[9]	Jun Wu, Junhong Zhang, Menghui Huang, Minhui Zhu, Zaikang Tong. Expression analysis of miR164 and its target gene NAC1 in response to low nitrate availability in Betula luminifera [J]. HEREDITAS(Beijing), 2016, 38(2): 155-162.
[10]	Xue Zhou, Yilan Du, Ping Jin, Fei Ma. Bioinformatic analysis of cancer-related microRNAs and their target genes [J]. HEREDITAS(Beijing), 2015, 37(9): 855-864.
[11]	Xiang Fang, Ningqiu Li, Xiaozhe Fu, Kaibin Li, Qiang Lin, Lihui Liu, Cunbin Shi, Shuqin Wu. Construction and application of bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer [J]. HEREDITAS(Beijing), 2015, 37(7): 702-710.
[12]	Hongmei Qiu, Wenyuan Hao, Shuqin Gao, Xiaoping Ma, Yuhong Zheng, Fanfan Meng, Xuhong Fan, Yang Wang, Yueqiang Wang, Shuming Wang. Gene mining of sulfur-containing amino acid metabolic enzymes in soybean [J]. HEREDITAS(Beijing), 2014, 36(9): 934-942.
[13]	Yang Shi, Xiao Xu, Haoyang Li, Qian Xu, Jichen Xu. Bioinformatics analysis of the expansin gene family in rice [J]. HEREDITAS(Beijing), 2014, 36(8): 809-820.
[14]	Lu Qi, Yanqing Ding. Involvement of the CREB5 regulatory network in colorectal cancer metastasis [J]. HEREDITAS(Beijing), 2014, 36(7): 679-684.
[15]	Xianzhi Chen, Yan Wang, Jianlei Shi, Longjing Zhu, Kelei Wang, Jian Xu. Genome-wide identification, sequence characteristic and expression analysis of heat shock factors (HSFs) in cucumber [J]. HEREDITAS, 2014, 36(4): 376-386.