Prolactin-Responsive Circular RNA circHIPK3 Promotes Proliferation of Mammary Epithelial Cells from Dairy Cow.

Hu Xu,Yanhong Wang,Dewei Li,Hong Chen,Linghao Kong,Xingtang Fang,Menglu Li,Chunlei Zhang,Jia Liu,Mengwen Cao,Molan Zhang,Chengchuang Song

doi:10.3390/genes11030336

Abstract

The highly expressed circHIPK3 is a circular RNA that has been previously reported to regulate the growth of human cells. In this study, we found an increased expression of circHIPK3 in bovine mammary epithelial cells treated with prolactin (PRL) in high-throughput sequencing data. Thus, we further investigated the effect of circHIPK3 on the proliferation and differentiation of mammary epithelial cells. We used qRT-PCR/Cell Counting Kit-8 (CCK-8) and a Western blotting analysis to evaluate the effects on cell proliferation. We found that circHIPK3 promotes the proliferation of mammary epithelial cells. The STAT5 signaling pathway was previously associated with the prolactin response and when the STAT5 was suppressed, the expression of circHIPK3 decreased. The results suggest that the response to prolactin and the associated STAT5 signaling pathway affect the expression of circHIPK3, which subsequently affects the proliferation of mammary epithelial cells in dairy cows.

Highlights

Lactation persistency (LP) influences the overall milk production of dairy cattle and animal health, making it an economically important trait for dairy cattle
The circHIPK3 is derived from exon2 of the HIPK3 gene and is an important circRNA involved in the proliferation and differentiation of several kinds of human cells [16]
CircHIPK3 can promote the proliferation and differentiation of chicken myoblast cells [19], and inhibit the apoptosis of human osteoblasts [29]. These results led us to question whether circHIPK3 plays an important role in the mammary gland

Summary

Introduction

Lactation persistency (LP) influences the overall milk production of dairy cattle and animal health, making it an economically important trait for dairy cattle. The number and activity of milk-secreting cells determines the persistency of lactation [1]. Prolactin (PRL) plays a key role during pregnancy and the postpartum development of the mammary gland for successful lactation [2]. PRL is a key regulator of the mammalian reproductive process but is involved in the process of breast proliferation and differentiation during pregnancy [3,4]. Chronic administration of the PRL-release inhibitor quinagolide can suppress cell proliferation and enhance apoptosis in the mammary tissue of lactating dairy cows [5], whereas PRL injections lead to a higher cell proliferation rate. Treated with quinagolide injection can reduce the apoptosis of mammary epithelial cells in lactating dairy cows [6]. PRL acts to stimulate the proliferation of bovine mammary gland epithelial cells [7]

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