J Cancer 2020; 11(3):599-609. doi:10.7150/jca.35041

Research Paper

CircRNA_100395 inhibits cell proliferation and metastasis in ovarian cancer via regulating miR-1228/p53/epithelial-mesenchymal transition (EMT) axis

Xian Li1*✉, Shuihua Lin2*, Zhifeng Mo3, Jinxing Jiang4, Haifeng Tang5, Cailin Wu6, Jian Song7

1. Department of Obstetrics and Gynaecology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong, China.
2. Department of Medical Imaging, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong, China.
3. Department of Emergency & Disaster Medical Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.
4. Cytotherapy Laboratory, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.
5. Department of Obstetrics and Gynaecology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong, China.
6. Department of Obstetrics and Gynaecology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong, China.
7. Department of Obstetrics and Gynaecology, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong, China.
*These authors contributed equally to this work.

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Citation:
Li X, Lin S, Mo Z, Jiang J, Tang H, Wu C, Song J. CircRNA_100395 inhibits cell proliferation and metastasis in ovarian cancer via regulating miR-1228/p53/epithelial-mesenchymal transition (EMT) axis. J Cancer 2020; 11(3):599-609. doi:10.7150/jca.35041. Available from http://www.jcancer.org/v11p0599.htm

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Abstract

Purpose: Circular RNAs (circRNAs) have been reported to regulate the incidence of tumor by regulating the transcriptional level and post-transcriptional level of tumor-related genes, and are significantly correlated with tumor metastasis and progression. CircRNA_100395 (circ_100395) has been reported to suppress lung cancer cell proliferation, and might act as an oncogene in deveopment of various cancers. However, the expression and function of circ_100395 in ovarian cancer has not been systematically researched.

Methods: The expression of circ_100395 in ovarian cancer tissues was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between circ_100395 expression and clinicopathological characteristics was further analyzed. After increasing the expression of circ_100395 by plasmid transfection in ovarian cancer cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among circ_100395, miR-1228 and p53 in ovarian cancer, was explored by luciferase reporter assay.

Results: The expression of circ_100395 was found to be significantly down-regulated in ovarian cancer, while low expression of circ_100395 was highly correlated with the poor outcomes. In addition, upregulation of circ_100395 could significantly inhibit tumor growth, metastasis and EMT signaling pathway in ovarian cancer. Furthermore, the expression level of circ_100395 was negatively correlated with the expression of miR-1228, and with the addition of miR-1228 could reverse anti-cell proliferation effect induced by circ_100395 in ovarian cancer cells. In addition, p53 might be the key target of circ_100395 / miR-1228 axis in ovarian cancer.

Conclusion: CircRNA_100395 could inhibit cell growth and metastasis of ovarian cancer cells via regulating the miR-1228/p53/EMT axis.

Keywords: CircRNA_100395, Cell Growth, Metastasis, EMT, Ovarian Cancer.