Upregulated LINC00565 Accelerates Ovarian Cancer Progression By Targeting GAS6

Mi Gong; Chengyan Luo; Huangyang Meng; Siyue Li; Sipei Nie; Yi Jiang; Yicong Wan; Huijian Li; Wenjun Cheng

doi:10.2147/OTT.S227758

Upregulated LINC00565 Accelerates Ovarian Cancer Progression By Targeting GAS6

Onco Targets Ther. 2019 Nov 20:12:10011-10022. doi: 10.2147/OTT.S227758. eCollection 2019.

Authors

Mi Gong^#^{1

2}, Chengyan Luo^#¹, Huangyang Meng^#¹, Siyue Li¹, Sipei Nie¹, Yi Jiang¹, Yicong Wan¹, Huijian Li^{3

4

5}, Wenjun Cheng¹

Affiliations

¹ Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, People's Republic of China.
² Department of Gynecology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, People's Republic of China.
³ State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China.
⁴ Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China.
⁵ Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi, Jiangsu 214002, People's Republic of China.

^# Contributed equally.

Abstract

Background: Long noncoding RNAs (lncRNAs) have been identified to participate in tumorigenesis. However, the underlying mechanisms of differentially expressed lncRNAs engaged in diseases remain indistinct and need further exploration.

Methods: Raw data files downloaded from TCGA and GEO dataset were used to analyze the differentially expressed lncRNAs and LINC00565 was picked out as the potential oncogene. qRT-PCR was used to analyze the LINC00565 level in ovarian tissues and cell lines. Subsequently, the selected ovarian tumor cells were then transfected with LINC00565 siRNA by Lipofectamine 2000 and the cell cycle was detected by flow cytometry. Effect of LINC00565 on tumor growth and cell cycle was verified by tumor formation assay in nude mice. The mechanism of LINC00565 involving in cell cycle regulation was further explored by Western blot.

Results: In this research, we discovered that LINC00565, a novel lncRNA, was highly expressed in ovarian cancer (OC). LINC00565 expression level was negatively associated with outcomes of OC patients. Further analysis showed that LINC00565 expression was closely correlated to tumor size, FIGO stage, but not related to other clinical features. In vitro experiments indicated that knockdown of LINC00565 significantly inhibited proliferative, invasive and migratory abilities of ovarian cancer cells. Besides, knockdown of LINC00565 can induce cell cycle arrest in G0/G1 phase. In addition, in vivo assay showed that low expression of LINC00565 inhibited the growth of OC. Further study found that LINC00565 knockdown markedly downregulated the protein expressions of CyclinD1, CyclinE1 and CDK4, but upregulated the expression of P16 and P21. Subsequently, we confirmed that LINC00565 promoted the progression of OC via upregulating GAS6, which has been confirmed to promote tumor progression.

Conclusion: In summary, our study firstly reported that the LINC00565 functioned as an oncogene to promote the progression of OC by interacting with GAS6.

Keywords: GAS6; LINC00565; OC; cell cycle; ovarian cancer.