Department of Health, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi Province, PR China.
Department of Reproductive Health, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi Province, PR China.
Cell Biol Int. 2021 Jul;45(7):1487-1497. doi: 10.1002/cbin.11588. Epub 2021 May 16.
Long noncoding RNA HOTTIP is a crucial regulator in multiple types of cancer, including ovarian cancer (OC). However, the biological roles and underlying mechanisms of HOTTIP in OC have rarely been studied. Hence, this study aimed to investigate the functional correlation between HOTTIP and pyroptosis in OC progression. The expression of HOTTIP in OC tissues and cell lines was characterized by quantitative real-time PCR. Cell proliferation was evaluated using Cell Counting Kit-8 and clone formation assays. Western blot was performed to quantify protein levels. A dual-luciferase reporter assay was used to analyze the molecular interaction among HOTTIP, miR-148a-3p, and AKT2. The expression of HOTTIP was significantly upregulated in OC tissue samples and cell lines. The silencing of HOTTIP led to the inhibition of cell proliferation and NLRP1 inflammasome-mediated pyroptosis. In addition, HOTTIP increased AKT2 expression by negatively regulating miR-148a-3p and then inhibited ASK1/JNK signaling. Further rescue experiments revealed that downregulation of miR-148a-3p and overexpression of AKT2 obviously diminished the effects of HOTTIP downregulation in OC cells. Thus, our study elucidated a novel pyroptosis-related mechanism by which HOTTIP participated in OC progression, which might provide a theoretical reference for clinical treatment.
长链非编码 RNA HOTTIP 是多种癌症（包括卵巢癌[OC]）的关键调节因子。然而，HOTTIP 在 OC 中的生物学作用和潜在机制很少被研究。因此，本研究旨在探讨 HOTTIP 在 OC 进展过程中与细胞焦亡之间的功能相关性。采用实时定量 PCR 检测 OC 组织和细胞系中 HOTTIP 的表达。通过细胞计数试剂盒-8 和克隆形成实验评估细胞增殖。采用 Western blot 检测蛋白水平。采用双荧光素酶报告基因实验分析 HOTTIP、miR-148a-3p 和 AKT2 之间的分子相互作用。OC 组织样本和细胞系中 HOTTIP 的表达明显上调。沉默 HOTTIP 导致细胞增殖和 NLRP1 炎性体介导的细胞焦亡受到抑制。此外，HOTTIP 通过负调控 miR-148a-3p 增加 AKT2 的表达，从而抑制 ASK1/JNK 信号通路。进一步的挽救实验表明，下调 miR-148a-3p 和过表达 AKT2 明显减弱了 HOTTIP 下调对 OC 细胞的影响。因此，本研究阐明了 HOTTIP 参与 OC 进展的一种新的细胞焦亡相关机制，可为临床治疗提供理论参考。
