LncRNA HOTTIP promotes the proliferation and invasion of ovarian cancer cells by activating the MEK/ERK pathway

Liu,Jian; Hu,Hong‑Bo; Liu,Yan‑Ming; Li,Fan‑Xiang; Zhang,Liu‑Ping; Liao,Zong‑Min

doi:10.3892/mmr.2020.11452

LncRNA HOTTIP promotes the proliferation and invasion of ovarian cancer cells by activating the MEK/ERK pathway

Authors:
- Jian Liu
- Hong‑Bo Hu
- Yan‑Ming Liu
- Fan‑Xiang Li
- Liu‑Ping Zhang
- Zong‑Min Liao
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Affiliations: 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
Published online on: August 21, 2020 https://doi.org/10.3892/mmr.2020.11452
Pages: 3667-3676
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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