Full Text:   <2646>

Summary:  <2076>

CLC number: R735.2

On-line Access: 2017-01-03

Received: 2016-05-10

Revision Accepted: 2016-08-01

Crosschecked: 2016-12-13

Cited: 1

Clicked: 4575

Citations:  Bibtex RefMan EndNote GB/T7714


Zhong-dong Wang


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.1 P.27-36


Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells

Author(s):  Zhong-dong Wang, Fan-yong Qu, Yuan-yuan Chen, Zhang-shen Ran, Hai-yan Liu, Hai-dong Zhang

Affiliation(s):  Clinical Laboratory of Taishan Sanatorium of Shandong Province, Tai’an 271001, China; more

Corresponding email(s):   zdongwang@yeah.net

Key Words:  miR-718, MicroRNA, Early growth response protein 3 (EGR3), Hepatocellular carcinoma (HCC), Malignant phenotype

Zhong-dong Wang, Fan-yong Qu, Yuan-yuan Chen, Zhang-shen Ran, Hai-yan Liu, Hai-dong Zhang. Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells[J]. Journal of Zhejiang University Science B, 2017, 18(1): 27-36.

@article{title="Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells",
author="Zhong-dong Wang, Fan-yong Qu, Yuan-yuan Chen, Zhang-shen Ran, Hai-yan Liu, Hai-dong Zhang",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells
%A Zhong-dong Wang
%A Fan-yong Qu
%A Yuan-yuan Chen
%A Zhang-shen Ran
%A Hai-yan Liu
%A Hai-dong Zhang
%J Journal of Zhejiang University SCIENCE B
%V 18
%N 1
%P 27-36
%@ 1673-1581
%D 2017
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600205

T1 - Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells
A1 - Zhong-dong Wang
A1 - Fan-yong Qu
A1 - Yuan-yuan Chen
A1 - Zhang-shen Ran
A1 - Hai-yan Liu
A1 - Hai-dong Zhang
J0 - Journal of Zhejiang University Science B
VL - 18
IS - 1
SP - 27
EP - 36
%@ 1673-1581
Y1 - 2017
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600205

Objective: hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. microRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods: Here we first used a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.


方法:采用聚合酶链反应(PCR)方法构建miR-718和EGR3的过表达及敲降质粒,并采用实时定量PCR(qRT-PCR)方法验证质粒有效性;采用MTT法和克隆形成实验检测肝癌细胞系HepG2和SMMC-7721的生长增殖能力;采用Transwell迁移侵袭实验检测肝癌细胞系HepG2和SMMC-7721的迁移和侵袭能力;采用增强型绿色荧光蛋白(EGFP)荧光报告载体实验验证miR-718的靶基因;采用qRT-PCR和蛋白质印迹(Western blot)检测相关基因表达水平的变化。
结论:miR-718在肝癌细胞系HepG2和SMMC-7721中起到抑癌基因的作用;EGR3在肝癌细胞系 HepG2和SMMC-7721中起到促癌基因的作用;miR-718是通过靶定EGR3 mRNA 3’ UTR下调EGR3的表达起到抑癌基因的作用。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Ameres, S.L., Zamore, P.D., 2013. Diversifying microRNA sequence and function. Nat. Rev. Mol. Cell Biol., 14(8):475-488.

[2]Baron, V.T., Pio, R., Jia, Z., et al., 2015. Early growth response 3 regulates genes of inflammation and directly activates IL6 and IL8 expression in prostate cancer. Br. J. Cancer, 112(4):755-764.

[3]Bartel, D.P., 2009. MicroRNAs: target recognition and regulatory functions. Cell, 136(2):215-233.

[4]Bronte, F., Bronte, G., Fanale, D., et al., 2015. Hepatomirnoma: the proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma. Crit. Rev. Oncol. Hematol., 97:312-321.

[5]Fang, F., Shangguan, A.J., Kelly, K., et al., 2013. Early growth response 3 (Egr-3) is induced by transforming growth factor-β and regulates fibrogenic responses. Am. J. Pathol., 183(4):1197-1208.

[6]Farazi, T.A., Juranek, S.A., Tuschl, T., 2008. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development, 135(7):1201-1214.

[7]Felekkis, K., Touvana, E., Stefanou, C., et al., 2010. MicroRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia, 14(4):236-240.

[8]Fong, Z.V., Tanabe, K.K., 2014. The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer, 120(18):2824-2838.

[9]Gomez-Martin, D., Diaz-Zamudio, M., Galindo-Campos, M., et al., 2010. Early growth response transcription factors and the modulation of immune response: implications towards autoimmunity. Autoimmun. Rev., 9(6):454-458.

[10]Hu, X., Schwarz, J.K., Lewis, J.S., et al., 2010. A microRNA expression signature for cervical cancer prognosis, Cancer Res., 70(4):1441-1448.

[11]Kimhofer, T., Fye, H., Taylor-Robinson, S., et al., 2015. Proteomic and metabonomic biomarkers for hepatocellular carcinoma: a comprehensive review. Br. J. Cancer, 112(7):1141-1156.

[12]Leng, R., Zha, L., Tang, L., 2014. MiR-718 represses VEGF and inhibits ovarian cancer cell progression. FEBS Lett., 588(12):2078-2086.

[13]Li, L., Yun, S.H., Keblesh, J., et al., 2007. Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol. Cell. Neurosci., 35(1):76-88.

[14]Liao, F., Ji, M.Y., Shen, L., et al., 2013. Decreased Egr3 expression is related to poor prognosis in patients with gastric cancer. J. Mol. Histol., 44(4):463-468.

[15]Lin, M., Chen, W., Huang, J., et al., 2011. MicroRNA expression profiles in human colorectal cancers with liver metastases. Oncol. Rep., 25(3):739-747.

[16]Perez-Cadahia, B., Drobic, B., Davie, J.R., 2011. Activation and function of immediate-early genes in the nervous system. Biochem. Cell Biol., 89(1):61-73.

[17]Pio, R., Jia, Z., Baron, V.T., et al., 2013. Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer. PLoS ONE, 8(1):e54096.

[18]Shukla, G.C., Singh, J., Barik, S., 2011. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol. Cell. Pharmacol., 3(3):83-92.

[19]Singh, R., Yadav, V., Kumar, S., et al., 2015. MicroRNA-195 inhibits proliferation, invasion and metastasis in breast cancer cells by targeting FASN, HMGCR, ACACA and CYP27B1. Sci. Rep., 5:17454.

[20]Sugimachi, K., Matsumura, T., Hirata, H., et al., 2015. Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br. J. Cancer, 112(3):532-538.

[21]Suzuki, T., Inoue, A., Miki, Y., et al., 2007. Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor. Endocr. Relat. Cancer, 14(2):279-292.

[22]Waller, L.P., Deshpande, V., Pyrsopoulos, N., 2015. Hepatocellular carcinoma: a comprehensive review. World J. Hepatol., 7(26):2648-2663.

[23]Wan, H.Y., Li, Q.Q., Zhang, Y., et al., 2014. MiR-124 represses vasculogenic mimicry and cell motility by targeting amotL1 in cervical cancer cells. Cancer Lett., 355(1):148-158.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE