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Research Paper|Volume 12, Issue 5|pp 4558—4572

Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1

Junrong Wang1, Weimin Ding2,4, Yingke Xu1, Enfu Tao3, Miaojun Mo3, Wei Xu2, Xu Cai2, Xiaomin Chen1, Junhui Yuan3, Xiuying Wu2
  • 1Department of Laboratory Medicine, Wenling Maternal and Child Health Care Hospital, Wenling 317500, Zhejiang Province, China
  • 2Department of Obstetrics and Gynecology, Wenling Maternal and Child Health Care Hospital, Wenling 317500, Zhejiang Province, China
  • 3Department of Pediatrics, Wenling Maternal and Child Health Care Hospital, Wenling 317500, Zhejiang Province, China
  • 4Department of Obstetrics and Gynecology, Women’s Hospital School of Medicine Zhejiang University, Hangzhou 310000, Zhejiang Province, China
* Co-first authors
Received: December 31, 2019Accepted: March 4, 2020Published: March 12, 2020
https://doi.org/10.18632/aging.102911

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: In recent decades, long non-coding RNAs (lncRNAs) have been reported as crucial functional regulators involved in ovarian cancer. In the present study, we explored how lncRNA RHPN1-AS1 influences the progression of epithelial ovarian cancer (EOC) through tumor cell-dependent mechanisms.

Results: The expression of RHPN1-AS1 in EOC tissues was higher than that in para-cancerous control tissues. High expression of RHPN1-AS1 was closely associated with poor prognosis in EOC patients. N6-methyladenosine (m6A) improved the stability of RHPN1-AS1 methylation transcript by reducing RNA degradation, which resulted in upregulation of RHPN1-AS1 in EOC. In vitro and in vivo functional experiments showed that RHPN1-AS1 promoted EOC cell proliferation and metastasis. RHPN1-AS1 acted as a ceRNA to sponge miR-596, consequently increasing LETM1 expression and activating the FAK/PI3K/Akt signaling pathway.

Conclusion: RHPN1-AS1-miR-596-LETM1 axis plays a crucial role in EOC progression. Our findings may provide promising drug targets for EOC treatment.

Methods: We determined the aberrantly expressed lncRNAs in EOC via microarray analysis and validated RHPN1-AS1 expression by qRT-PCR. The RHPN1-AS1-miR-596-LETM1 axis was examined by dual-luciferase reporter assay and RIP assay. The mechanism of RHPN1-AS1 was investigated through gain- and loss-of-function studies both in vivo and in vitro.