H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells

Sun,Hong; Wang,Guo; Peng,Yan; Zeng,Ying; Zhu,Qiong-Ni; Li,Tai-Lin; Cai,Jia-Qin; Zhou,Hong-Hao; Zhu,Yuan-Shan

doi:10.3892/or.2015.3899

H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells

Authors:
- Hong Sun
- Guo Wang
- Yan Peng
- Ying Zeng
- Qiong-Ni Zhu
- Tai-Lin Li
- Jia-Qin Cai
- Hong-Hao Zhou
- Yuan-Shan Zhu
View Affiliations

Affiliations: Department of Clinical Pharmacology, Xiangya Hospital and Institute of Clinical Pharmacology, Central South University, and Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China, Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: April 3, 2015 https://doi.org/10.3892/or.2015.3899
Pages: 3045-3052

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Harvey JM, Clark GM, Osborne CK and Allred DC: Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 17:1474–1481. 1999.PubMed/NCBI
3	Stender JD, Frasor J, Komm B, Chang KC, Kraus WL and Katzenellenbogen BS: Estrogen-regulated gene networks in human breast cancer cells: Involvement of E2F1 in the regulation of cell proliferation. Mol Endocrinol. 21:2112–2123. 2007. View Article : Google Scholar : PubMed/NCBI
4	Osborne CK: Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat. 51:227–238. 1998. View Article : Google Scholar
5	Katzenellenbogen BS, Montano MM, Ediger TR, et al: Estrogen receptors: Selective ligands, partners, and distinctive pharmacology. Recent Prog Horm Res. 55:163–195. 2000.PubMed/NCBI
6	Frasor J, Danes JM, Komm B, Chang KC, Lyttle CR and Katzenellenbogen BS: Profiling of estrogen up- and down-regulated gene expression in human breast cancer cells: Insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology. 144:4562–4574. 2003. View Article : Google Scholar : PubMed/NCBI
7	Stossi F, Barnett DH, Frasor J, Komm B, Lyttle CR and Katzenellenbogen BS: Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: Distinct and common target genes for these receptors. Endocrinology. 145:3473–3486. 2004. View Article : Google Scholar : PubMed/NCBI
8	Li CH and Chen Y: Targeting long non-coding RNAs in cancers: Progress and prospects. Int J Biochem Cell Biol. 45:1895–1910. 2013. View Article : Google Scholar : PubMed/NCBI
9	Pauli A, Rinn JL and Schier AF: Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet. 12:136–149. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ponting CP, Oliver PL and Reik W: Evolution and functions of long noncoding RNAs. Cell. 136:629–641. 2009. View Article : Google Scholar : PubMed/NCBI
11	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
12	Prensner JR and Chinnaiyan AM: The emergence of lncRNAs in cancer biology. Cancer Discov. 1:391–407. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bartolomei MS, Zemel S and Tilghman SM: Parental imprinting of the mouse H19 gene. Nature. 351:153–155. 1991. View Article : Google Scholar : PubMed/NCBI
14	Ariel I, de Groot N and Hochberg A: Imprinted H19 gene expression in embryogenesis and human cancer: The oncofetal connection. Am J Med Genet. 91:46–50. 2000. View Article : Google Scholar : PubMed/NCBI
15	Glaser T, Housman D, Lewis WH, Gerhard D and Jones C: A fine-structure deletion map of human chromosome 11p: Analysis of J1 series hybrids. Somat Cell Mol Genet. 15:477–501. 1989. View Article : Google Scholar : PubMed/NCBI
16	Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A and Galun E: The H19 non-coding RNA is essential for human tumor growth. PLoS One. 2:e8452007. View Article : Google Scholar : PubMed/NCBI
17	Luo M, Li Z, Wang W, Zeng Y, Liu Z and Qiu J: Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett. 333:213–221. 2013. View Article : Google Scholar : PubMed/NCBI
18	Adriaenssens E, Dumont L, Lottin S, Bolle D, Leprêtre A, Delobelle A, Bouali F, Dugimont T, Coll J and Curgy JJ: H19 overexpression in breast adenocarcinoma stromal cells is associated with tumor values and steroid receptor status but independent of p53 and Ki-67 expression. Am J Pathol. 153:1597–1607. 1998. View Article : Google Scholar : PubMed/NCBI
19	Lottin S, Adriaenssens E, Dupressoir T, Berteaux N, Montpellier C, Coll J, Dugimont T and Curgy JJ: Overexpression of an ectopic H19 gene enhances the tumorigenic properties of breast cancer cells. Carcinogenesis. 23:1885–1895. 2002. View Article : Google Scholar : PubMed/NCBI
20	Berteaux N, Lottin S, Monté D, Pinte S, Quatannens B, Coll J, Hondermarck H, Curgy JJ, Dugimont T and Adriaenssens E: H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem. 280:29625–29636. 2005. View Article : Google Scholar : PubMed/NCBI
21	Adriaenssens E, Lottin S, Dugimont T, Fauquette W, Coll J, Dupouy JP, Boilly B and Curgy JJ: Steroid hormones modulate H19 gene expression in both mammary gland and uterus. Oncogene. 18:4460–4473. 1999. View Article : Google Scholar : PubMed/NCBI
22	Tsang WP and Kwok TT: Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 26:4877–4881. 2007. View Article : Google Scholar : PubMed/NCBI
23	Tan C, Cai LQ, Wu W, Qiao Y, Imperato-McGinley J, Chen GQ and Zhu YS: NSC606985, a novel camptothecin analog, induces apoptosis and growth arrest in prostate tumor cells. Cancer Chemother Pharmacol. 63:303–312. 2009. View Article : Google Scholar
24	Brannan CI, Dees EC, Ingram RS and Tilghman SM: The product of the H19 gene may function as an RNA. Mol Cell Biol. 10:28–36. 1990.PubMed/NCBI
25	Gabory A, Jammes H and Dandolo L: The H19 locus: Role of an imprinted non-coding RNA in growth and development. BioEssays. 32:473–480. 2010. View Article : Google Scholar : PubMed/NCBI
26	Hao Y, Crenshaw T, Moulton T, Newcomb E and Tycko B: Tumour-suppressor activity of H19 RNA. Nature. 365:764–767. 1993. View Article : Google Scholar : PubMed/NCBI
27	Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS and Penn LZ: The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res. 66:5330–5337. 2006. View Article : Google Scholar : PubMed/NCBI
28	Doucrasy S, Coll J, Barrois M, Joubel A, Prost S, Dozier C, Stehelin D and Riou G: Expression of the human fetal bac h19 gene in invasive cancers. Int J Oncol. 2:753–758. 1993.PubMed/NCBI
29	Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D and Coll J: The H19 gene is expressed within both epithelial and stromal components of human invasive adenocarcinomas. Biol Cell. 85:117–124. 1995. View Article : Google Scholar : PubMed/NCBI