Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Huaian Maternal and Child Health Hospital, Huaian City, Jiangsu Province, China.
Biotechnol Genet Eng Rev. 2023 Oct;39(2):1128-1142. doi: 10.1080/02648725.2023.2167772. Epub 2023 Jan 26.
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 ( < 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.
长链非编码 RNA LINC02489 在晚期卵巢癌（OC）中显示出明显下调。然而，LINC02489 的功能仍然未知。本研究旨在解释 LINC02489 在 OC 中的作用和机制。通过 qRT-PCR 检测原发性 OC 组织中 LINC02489 的表达。此外，还使用 MTT、划痕愈合、transwell 和流式细胞术检测分析 LINC02489 的功能。通过高通量 RNA-seq、qRT-PCR、western blot 和 N6-甲基腺苷（m6A）meRIP 研究 LINC02489 在 OC 中的机制。转移性和耐药 OC 组织中分别有 1101 个和 827 个基因显著下调和上调。与原发性 OC 组织相比，转移性和耐药 OC 组织中 LINC02489 的表达降低（<0.05）。过表达 LINC02489 可抑制耐药 OC 细胞的增殖、侵袭和迁移。在过表达 LINC02489 的耐药 SKOV3 细胞中，m6A 修饰的 LINC02489 显著上调。此外，过表达 LINC02489 可增加 PKNOX2 的表达，同时降低 PTEN 和 mTOR 的表达。本研究表明，LINC02489 通过增加其 m6A 修饰和上调 PKNOX2 的表达，抑制耐药 OC 细胞的侵袭和迁移。此外，LINC02489 通过 PTEN/mTOR 信号通路调节 OC 细胞的侵袭能力，从而调节 SKOV3 细胞对紫杉醇的敏感性。该结果为耐药 OC 提供了一个潜在的治疗靶点。
