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A Novel Micro RNA Feedback Loop of High Mobility Group Protein A1a in Regulating Estrogen Receptor Alpha Alternative Splicing

Volume 11 - Issue 1

Kenji Ohe1*, Yoshihiro Harada1, Yuta Horita1, Hiroyoshi Harada1, Hiroki Terai1, Masayoshi Mori1, Yusuke Murata1, Kenji Ashida2, Munechika Enjoji1

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    • 1Department of Pharmacotherapeutics, Faculty of Phamaceutical Sciences, Fukuoka University, Fukuoka city, Japan
    • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume city, Japan
    • *Corresponding author: Kenji Ohe, Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Japan

Received: May 31, 2018;   Published: November 16, 2018

DOI: 10.26717/BJSTR.2018.11.002058

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The hERα gene is known for its major role in estrogen dependent growth of breast cancer. ERα positivity is a hallmark in treating these cancers. Though there are many isoforms reported for hERα, the splicing regulation, especially for the 5’ non-coding exons is largely unknown. We have recently reported that the oncogenic product, high-mobility-group protein A1a (HMGA1a) can induce the expression of hERα46 through regulating alternative splicing of the hERα gene. An RNA decoy of HMGA1a can reverse this splicing event as well as alter estrogen responsiveness of MCF-7 breast cancer cells. Here, we will review on the emerging issue of HMGA1a as a sequence-specific RNA-binding protein and show experimental evidence of the HMGA1a RNA-binding site found in the seed sequence of a microRNA and possible feedback loop.

Keywords : ERα Gene; Hmga1a; Non Coding Exon; Splicing Regulation; Microrna; Tamoxifen Resistance

Abbreviations : HERα: Human Estrogen Receptor Alpha; HGRα: Human Glucocorticoid Receptor Alpha; HMGA1a: High Mobility Group Protein A1a; HPS2: Human Presenilin-2; PR: Progesterone Receptor; FOS: FBJ Murine Osteosarcoma Viral Oncogene Homolog; TFF1: Trefoil Factor 1; ERBB2: v-erb-b2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2; Her2, Human Epidermal Growth Factor Receptor 2; miR-16: MicroRNA 16; mir-21: microRNA 21; RNU-6: U6 Small Nuclear RNA

Materials and Methods| Introduction| Results| Discussion| Author contributions| References|