Int J Biol Sci 2020; 16(1):99-115. doi:10.7150/ijbs.35643

Research Paper

Long non-coding RNA steroid receptor activator promotes the progression of endometrial cancer via Wnt/ β-catenin signaling pathway

Sun-Ae Park1, Lee Kyung Kim1, Young Tae Kim2✉, Tae-Hwe Heo1✉, Hee Jung Kim1✉

1. Laboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Seoul, 03722, Republic of Korea
2. Institute of Women's Life Medical Science, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

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Citation:
Park SA, Kim LK, Kim YT, Heo TH, Kim HJ. Long non-coding RNA steroid receptor activator promotes the progression of endometrial cancer via Wnt/ β-catenin signaling pathway. Int J Biol Sci 2020; 16(1):99-115. doi:10.7150/ijbs.35643. Available from http://www.ijbs.com/v16p0099.htm

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Abstract

Rationale: Steroid receptor activator (SRA), a long non-coding RNA, serves as a critical regulator of gynecologic cancer. The objective of this study was to determine biological function and clinical significance of SRA expression in endometrial cancer.

Method: We investigated whether SRA was involved in the development of endometrial cancer via binding to eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1) as a transcription factor to enhance Wnt/ β-catenin signaling pathway.

Results: Expression levels of SRA were upregulated in endometrial cancer tissues compared to those in adjacent control tissues. We also found high expression of SRA in EC cells. The relationship between SRA and EIF4E-BP1 was corroborated by transfection of a luciferase reporter plasmid. In addition, SRA knockdown inhibited the expression of EIF4E-BP1 known to play a critical role in the control of protein synthesis, cell growth, and cell survival, thus promoting tumourigenesis and epithelial-mesenchymal transition (EMT) important for cell motility and metastasis. Consistently, immunostaining and western blotting analysis showed that expression levels of β-catenin and 4EBP1 in the nucleus were significantly decreased by SRA knockdown but increased by SRA over-expression.

Conclusions: These results suggest that SRA is involved in proliferation, migration, and invasion of endometrial cancer cells by increasing the expression of EIF4E-BP1 and activity of Wnt/ β-catenin signaling. These findings indicate that SRA might be a novel biomarker for predicting recurrence and prognosis. It might also serve as a promising therapeutic target in endometrial cancer.

Keywords: Endometrial cancer (EC), Steroid Receptor Activator (SRA), Signaling pathway, Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1), Wnt/ β-catenin signaling