Oncotarget

Research Papers:

Involvement of miR-106b in tumorigenic actions of both prolactin and estradiol

Kuan-Hui Ethan Chen, Karissa Bustamante, Vi Nguyen and Ameae M. Walker _

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Oncotarget. 2017; 8:36368-36382. https://doi.org/10.18632/oncotarget.16755

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Abstract

Kuan-Hui Ethan Chen1, Karissa Bustamante1, Vi Nguyen1, Ameae M. Walker1

1Division of Biomedical Sciences, University of California, Riverside, CA 92521, USA

Correspondence to:

Ameae M. Walker, email: ameae.walker@ucr.edu

Keywords: miR-106b, prolactin, estradiol, p21, breast and prostate cancer

Received: February 04, 2017     Accepted: March 21, 2017     Published: March 31, 2017

ABSTRACT

Prolactin promotes a variety of cancers by an array of different mechanisms. Here, we have investigated prolactin’s inhibitory effect on expression of the cell cycle-regulating protein, p21. Using a miRNA array, we identified a number of miRNAs upregulated by prolactin treatment, but one in particular that was strongly induced by prolactin and predicted to bind to the 3′UTR of p21 mRNA, miR-106b. By creating a p21 mRNA 3′UTR-luciferase mRNA construct, we demonstrated degradation of the construct in response to prolactin in human breast, prostate and ovarian cancer cell lines. Increased expression of miR-106b replicated, and anti-miR-106b counteracted, the effects of prolactin on degradation of the 3′UTR construct, p21 mRNA levels, and cell proliferation in breast (T47D) and prostate (PC3) cancer cells. Increased expression of miR-106b also stimulated migration of the very epithelioid T47D cell line. By contrast, anti-miR-106b dramatically decreased expression of the mesenchymal markers, SNAIL-2, TWIST-2, VIMENTIN, and FIBRONECTIN. Using signaling pathway inhibitors and the 3′UTR construct, induction of miR-106b by prolactin was determined to be mediated through the MAPK/ERK and PI3K/Akt pathways and not through Jak2/Stat5 in both T47D and PC3 cells. Prolactin activation of MAPK/ERK and PI3K/Akt also activates ERα in the absence of an ERα ligand. 17β-estradiol promoted degradation of the construct in both cell lines and pre-incubation in the estrogen antagonist, Fulvestrant, blocked the ability of both prolactin and 17β-estradiol to induce the construct-degrading activity. Together, these data support a convergence of the prolactin and 17β-estradiol miR-106b-elevating signaling pathways at ERα.


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