LINC02489 with m6a modification increase paclitaxel sensitivity by inhibiting migration and invasion of ovarian cancer cells

Abstract

ABSTRACT The long non-coding RNA LINC02489 has been shown to be significantly downregulated in advanced ovarian cancer (OC). However, the function of LINC02489 remains unknown. This study aims to explain the role and mechanism of LINC02489 in OC. The expression of LINC02489 was examined by qRT-PCR in primary OC tissues. Additionally, MTT, wound healing, transwell, and flow cytometry assays were used to analyze the function of LINC02489. The mechanism of LINC02489 in OC was investigated by high-throughput RNA-sequencing, qRT-PCR, western blot, and N6-methyladenosine (m6A) meRIP. A total of 1101 and 827 genes are significantly down-regulated and up-regulated in metastatic and chemoresistant OC tissues. The expression of LINC02489 is decreased in metastatic and chemoresistant OC tissues compared with the primary OC tissues (p < 0.05). Overexpression of LINC02489 inhibits proliferation, invasion, and migration of drug-resistant OC cells. In the LINC02489 overexpressed chemoresistant SKOV3 cells, the m6A modified LINC02489 is significantly up-regulated. Furthermore, the expression of PKNOX2 is increased during overexpression of LINC02489, while the expression of PTEN and mTOR plummets. This study demonstrates that LINC02489 can inhibit the invasion and migration of chemoresistant OC cells by increasing its m6A modification and up-regulating PKNOX2 expression. In addition, LINC02489 regulates the invasion ability of OC cells through the PTEN/mTOR signaling pathway, thereby regulating the sensitivity of SKOV3 cells to paclitaxel. This result provides a potential therapeutic target for chemoresistant OC.