Cheng Jiwen,Zhao Pu,Yang Weili,et al.Let-7b modulates the proliferation of hepatoblastoma cells by targeting SALL4[J].Journal of Clinical Pediatric Surgery,,19():404-409.[doi:10.3969/j.issn.1671-6353.2020.05.006]
Let-7b modulates the proliferation of hepatoblastoma cells by targeting SALL4
- Keywords:
- let-7b; Liver Neoplasms; SALL4; Cell Proliferation
- CLC:
- R726;R735.7
- Abstract:
- Objective To explore the role and mechanism of let-7b and SALL4 in the malignant behaviors of hepatoblastoma (HB) cells. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed for defecting the expression of let-7b in normal liver cells (HL-7702),HB cell lines,HB tissues and adjacent normal tissues.Immunohistochemistry was applied for measuring the expression levels of SALL4 in HB tissues and paracancerous tissue and analyzing the correlation between the expression levels of SALL4 in HB tissues.Up-regulating or inhibiting the let-7b expression level in HB cells was used for examining the effects of let-7b on the biological function of HB cells by methyl thiazolyl tetrazolium (MTT) assay,cell cycle and apoptosis.The targeting relationship between let-7b and SALL4 was assessed through dual-luciferase reporter system,qRT-PCR,Western blot and in vitro immunohistochemical staining. Results let-7b became markedly down-regulated in HB tissues and HB cells (e.g.HepG2 & HuH6) while SALL4 protein was frequently up-regulated in HB tissues.The expression of let-7b was correlated with PRETEXT stage (P=0.002).A significant negative correlation existed between let-7b and SALL4 expression level in HB tissue samples (r=-0.761,P<0.001).Through the detection of proliferative activity,cell cycle and cell apoptosis,let-7b could regulate the proliferating capability of HepG2.The dual-luciferase reporter assays revealed that SALL4 was a novel target of let-7b.Conclusion Serving as a tumor suppressor gene,let-7b suppresses the HepG2 cells growth by targeting SALL4.
References:
1 Spector LG,Birch J.The epidemiology of hepatoblastoma[J].Pediatr Blood Cancer,2012,59(5):776-779.DOI:10.1002/pbc.24215.
2 Bissig-Choisat B,Kettlun-Leyton C,Legras XD,et al.Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer[J].J Hepatol,2016,65(2):325-333.DOI:10.1016/j.jhep.2016.04.009.
3 Hooks KB,Audoux J,Fazli H,et al.New insights into diagnosis and therapeutic options for proliferative hepatoblastoma[J].Hepatology,2018,68(1):89-102.DOI:10.1002/hep.29672.
4 Sumazin P,Chen Y,Trevi?o LR,et al.Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups[J].Hepatology,2017,65(1):104-121.DOI:10.1002/hep.28888.
5 Axiotis CA,Monteagudo C,Merino MJ,et al.Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma[J].Am J Pathol,1991,138(4):799-806.
6 Wang Z,Xu L,Hu Y,et al.miRNA let-7b modulates macrophage polarization and enhances tumor-associated macrophages to promote angiogenesis and mobility in prostate cancer[J].Sci Rep,2016,6:25602.DOI:10.1038/srep25602.
7 Tian Y,Hao S,Ye M,et al.MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly[J].Biochem Biophys Res Commun,2015,458(2):307-312.DOI:10.1016/j.bbrc.2015.01.105.
8 Han X,Chen Y,Yao N,et al.MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1[J].Cancer Gene Ther,2015,22(3):122-129.DOI:10.1038/cgt.2014.75.
9 Saffari M,Ghaderian SMH,Omrani MD,et al.The Association of miR-let 7b and miR-548 with PTEN in Prostate Cancer[J].Urol J,2019,16(3):267-273.DOI:10.22037/uj.v0i0.4564.
10 Jin B,Wang W,Meng XX,et al.Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through regulating the epithelial-mesenchymal transition and the Wnt signaling pathway[J].BMC Cancer,2016,16(1):863.DOI:10.1186/s12885-016-2904-y.
11 Tian Y,Hao S,Ye M,et al.MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly[J].Biochem Biophys Res Commun,2015,458(2):307-312.DOI:10.1016/j.bbrc.2015.01.105.
12 Yong KJ,Gao C,Lim JS,et al.Oncofetal gene SALL4 in aggressive hepatocellular carcinoma[J].N Engl J Med,2013,368(24):2266-2276.DOI:10.1056/NEJMc1308785.
13 Tatetsu H,Kong NR,Chong G,et al.SALL4,the missing link between stem cells,development and cancer[J].Gene,2016,584(2):111-119.DOI:10.1016/j.gene.2016.02.019.
14 Zhou S,Venkatramani R,Gomulia E,et al.The diagnostic and prognostic value of SALL4 in hepatoblastoma[J].Histopathology,2016,69(5):822-830.DOI:10.1111/his.13005.
15 Tanimura N,Saito M,Ebisuya M,et al.Stemness-related factor Sall4 interacts with transcription factors Oct-3/4 and Sox2 and occupies Oct-Sox elements in mouse embryonic stem cells[J].J Biol Chem,2013,288(7):5027-5038.DOI:10.1074/jbc.M112.411173.
16 Yang J,Chai L,Liu F,et al.Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells[J].Proc Natl Acad Sci U S A,2007,104(25):10494-10499.DOI:10.1073/pnas.0704001104.
17 Liu C,Wu H,Li Y,et al.SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway[J].J Neurooncol,2017,135(2):263-272.DOI:10.1007/s11060-017-2589-3.
18 Hayashi S,Fujita K,Matsumoto S,et al.Isolation and identif ication of cancer stem cells from a side populat ion of a human hepatoblastoma cell line,HuH-6 clone-5[J].Pediatr Surg Int,2011,27(1):9-16.DOI:10.1007/s00383-010-2719-x.
Memo
收稿日期:2019-09-01。
基金项目:陕西省创新人才推进计划-青年科技新星项目(编号:2018KJXX-050);西安交通大学中央高校基本科研业务项目(编号:XTT2018126,YT(ZD)201704)
通讯作者:李鹏,Email:sienafiat@hotmail.com