Long Noncoding RNA CTD-2589M5.4 Inhibits Ovarian Cancer Cell Proliferation, Migration, and Invasion Via Downregulation of the Extracellular Matrix-Receptor Interaction Pathway.

Abstract

Background: The authors' previous study showed that the long noncoding RNA CTD-2589M5.4 was significantly upregulated in multidrug-resistant ovarian cancer cells. However, the role of CTD-2589M5.4 in the progression of ovarian cancer remains unclear. The purpose of this current study was to illuminate the biological function and possible mechanism of CTD-2589M5.4 in ovarian cancer development. Materials and Methods: The expression of CTD-2589M5.4 was examined via real-time quantitative PCR in primary ovarian cancer tissues (POCTs) and ovarian cancer cell lines. The biological function of CTD-2589M5.4 was analyzed via CCK-8 proliferation, wound healing, transwell, and flow cytometry assays in CTD-2589M5.4-overexpressed/silenced and control ovarian cancer cells. The mechanism of CTD-2589M5.4 function in ovarian cancer progression was analyzed utilizing high-throughput RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes analysis, qRT-PCR, Western blot, and rescue experiments. Results: CTD-2589M5.4 expression was decreased in the POCTs and ovarian cancer cells compared with the normal ovarian tissues (p < 0.05) and normal ovarian epithelial cells (p < 0.05). Overexpression of CTD-2589M5.4 inhibited the proliferation, invasion, and migration of ovarian cancer cells, while knockdown of CTD-2589M5.4 had the opposite effect. Furthermore, a total of 750 and 233 genes were notably upregulated and downregulated, respectively, in the CTD-2589M5.4-overexpressed A2780 cells, while the extracellular matrix (ECM)-receptor interaction pathway was significantly downregulated. In addition, overexpression of fibronectin 1 significantly abrogated the tumor suppressive function of CTD-2589M5.4. Conclusions: This study demonstrated that CTD-2589M5.4 could inhibit ovarian cancer cell proliferation, invasion, and migration, at least partially by way of downregulating the ECM-receptor interaction pathway, therefore providing a potential therapeutic target for the prevention and/or treatment of ovarian cancer.