Department of Obstetrics and Gynecology, Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Obstetrics and Gynecology, Hebei General Hospital, Shijiazhuang, China.
J Obstet Gynaecol Res. 2024 Dec;50(12):2271-2279. doi: 10.1111/jog.16077. Epub 2024 Oct 10.
The purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC).
We used matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR-545-3p, and MT1M in EOC patients were evaluated by quantitative real-time reverse transcriptase PCR (RT-qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan-Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion.
The promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum-resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression-free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR-545-3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR-545-3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells.
This research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients.
本实验旨在探讨长链非编码 RNA 261（LINC00261）基因在卵巢上皮性癌（EOC）化疗耐药及临床预后中的作用。
采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）检测 EOC 患者标本中 LINC00261 启动子区甲基化水平，实时荧光定量逆转录 PCR（RT-qPCR）检测 EOC 患者 LINC00261、miR-545-3p、MT1M 的表达水平。采用 Spearman 相关分析进行相关性分析，采用 Kaplan-Meier 法进行临床预后分析。构建稳定过表达 LINC00261 的 SKOV3 细胞株，检测 LINC00261 对 SKOV3 细胞增殖、铂类药物敏感性、迁移及侵袭的影响。
LINC00261 启动子区呈高甲基化状态，其在铂耐药 EOC 组织中表达明显下调。LINC00261 在 EOC 中的甲基化水平与其 RNA 表达呈显著负相关。此外，EOC 患者 LINC00261 高甲基化及低表达与无进展生存期（PFS）及总生存期（OS）缩短相关。Spearman 相关分析显示，miR-545-3p 的表达与 LINC00261 呈负相关。根据网站预测，MT1M 可能是 LINC00261 的下游靶基因。在 EOC 组织中，MT1M 的表达与 miR-545-3p 呈负相关，与 LINC00261 呈正相关。并且，MT1M mRNA 表达降低与化疗耐药及预后不良相关。体外实验结果表明，过表达 LINC00261 可抑制 SKOV3 细胞的顺铂耐药性、增殖能力，以及对迁移和侵袭的抑制作用。
本研究表明，LINC00261 的异常高甲基化和低表达与 EOC 患者铂类耐药和不良预后相关。
