Int J Biol Sci 2022; 18(5):1989-2002. doi:10.7150/ijbs.67486 This issue

Research Paper

LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer

Hui Lin1#, Xian Xu1#, Kelie Chen1#, Zhiqin Fu2, Shengchao Wang1, Yaqing Chen2, Honghe Zhang3, Yuequn Niu1, Hanwen Chen1,4, Hongfei Yu3, Jian-zhong Shao5, Weiguo Lu1, Yihua Wu1✉, Dajing Xia1✉

1. Department of Toxicology of School of Public Health, and Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China.
2. Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
3. Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
4. Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China.
5. College of Life Sciences, Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
#These authors have contributed equally to this work and share first authorship.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Lin H, Xu X, Chen K, Fu Z, Wang S, Chen Y, Zhang H, Niu Y, Chen H, Yu H, Shao Jz, Lu W, Wu Y, Xia D. LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer. Int J Biol Sci 2022; 18(5):1989-2002. doi:10.7150/ijbs.67486. Available from https://www.ijbs.com/v18p1989.htm

File import instruction

Abstract

Graphic abstract

Cancer Susceptibility Candidate 15 (CASC15), which is a newly identified long noncoding RNA crucial for epigenetic regulation in human tumors, was found to be associated with poor prognosis of the patients with ovarian cancer by utilizing The Cancer Genome Atlas and Gene Expression Omnibus database. Therefore, the purpose of this paper was to explore the functional role and latent molecular mechanism of CASC15 in the progression of ovarian cancer. In vitro and in vivo experiments validated CASC15 as an oncogenic lncRNA in ovarian cancer, which could enhance metastasis through TGF-β-induced epithelial-mesenchymal transition progress. MiR-23b-3p and miR-24-3p, which are members of the miR-23b cluster, were identified to directly target CASC15 through luciferase assays. Further mechanistic investigations indicated that CASC15-mediated miR-23b-3p/miR-24-3p sequestration cooperatively upregulated SMAD3 expression, which, in turn, would permit increased CASC15 mRNA level as a transcription activation factor. This study first described a miR-23b-3p/miR-24-3p-mediated positive feedback loop between CASC15 and SMAD3, which may reflect the underlying molecular mechanism of CASC15's oncogenic function in ovarian cancer.