Department of Gynaecology, Yuebei People's Hospital, Shaoguan, Guangdong 512026, P.R. China.
Department of Clinical Laboratory, Yuebei People's Hospital, Shaoguan, Guangdong 512026, P.R. China.
Mol Med Rep. 2020 Nov;22(5):3667-3676. doi: 10.3892/mmr.2020.11452. Epub 2020 Aug 21.
Recent studies have revealed that long non‑coding RNAs (lncRNAs) serve important roles in carcinogenesis and that this type of gene may be used as biomarkers in cancer. A high level of lncRNA HOXA distal transcript antisense RNA (HOTTIP) is associated with unfavorable prognosis for patients with ovarian cancer (OC), but the mechanism of HOTTIP involved in OC development remains to be elucidated. The present study aimed to investigate the mechanism of HOTTIP in metastasis‑associated OC cell behaviors. HOTTIP levels in ovarian cells were quantified by reverse transcription‑quantitative PCR, cell proliferation was analyzed by colony formation assay, and apoptosis was assessed by flow cytometry. Cell migratory and invasive abilities were evaluated by wound healing and Transwell assays, respectively. The expression levels of mitogen‑activated protein kinase kinase (MEK)/ERK pathway‑associated proteins were detected by western blotting. The results demonstrated that knockdown of HOTTIP in OC cells significantly reduced the phosphorylation levels of MEK and ERK, inhibited the proliferation and invasion of OC cells and promoted their apoptosis. Furthermore, the effects of HOTTIP on cell migration and invasion were partly associated with the epithelial‑mesenchymal transition (EMT) process. Proliferation, invasion and EMT of OC cells were enhanced following overexpression of HOTTIP; however, these effects were reversed by the MEK/ERK pathway inhibitor U0126. In conclusion, HOTTIP was demonstrated to promote the proliferation, migration and invasion of OC cells by activating the MEK/ERK pathway. Therefore, HOTTIP may serve as a potential therapeutic target for OC.
最近的研究表明，长非编码 RNA（lncRNA）在癌症发生中发挥重要作用，这种基因可能被用作癌症的生物标志物。高水平的 lncRNA HOXA 远端转录反义 RNA（HOTTIP）与卵巢癌（OC）患者的不良预后相关，但 HOTTIP 参与 OC 发展的机制仍有待阐明。本研究旨在探讨 HOTTIP 在转移相关 OC 细胞行为中的机制。通过逆转录定量 PCR 定量卵巢细胞中的 HOTTIP 水平，通过集落形成测定分析细胞增殖，通过流式细胞术评估细胞凋亡。通过划痕愈合和 Transwell 测定分别评估细胞迁移和侵袭能力。通过 Western blot 检测丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）通路相关蛋白的表达水平。结果表明，OC 细胞中 HOTTIP 的敲低显著降低了 MEK 和 ERK 的磷酸化水平，抑制了 OC 细胞的增殖和侵袭，并促进了其凋亡。此外，HOTTIP 对细胞迁移和侵袭的影响部分与上皮-间充质转化（EMT）过程有关。过表达 HOTTIP 增强了 OC 细胞的增殖、侵袭和 EMT；然而，这些作用被 MEK/ERK 通路抑制剂 U0126 逆转。总之，HOTTIP 通过激活 MEK/ERK 通路促进 OC 细胞的增殖、迁移和侵袭。因此，HOTTIP 可能成为 OC 的潜在治疗靶点。
