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Long non-coding RNA AOC4P suppresses epithelial ovarian cancer metastasis by regulating epithelial-mesenchymal
Xiaojing Lin1,2,3, Xiaoyan Tang1,3, Tingting Zheng1,3
1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, P.R. China.
Objective:
Currently, the function and mechanisms of long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer (EOC), especially those of the lncRNAs participated in the epithelial-mesenchymal transition (EMT) process, remains largely unknown. Here, we focused on a lncRNA named AOC4P and analysed its role in EOC.
Materials And Methods:
The expression of AOC4P gene was examined with quantitative real-time quantitative PCR (qRT-PCR). The cell migration and invasion were detected by Transwell and scratch assays. The in vivo metastatic activity was evaluated by intraperitoneal metastasis model. The downstream genes were investigated by a tumour EMT real-time polymerase chain reaction (RT-PCR) array, and validated by qRT-PCR and Western blot.
Results:
The results showed that AOC4P expression levels were decreased in EOC tissues and cell lines, and that the under-expression of AOC4P was positively correlated with FIGO stage and lymph node metastasis. Furthermore, the knockdown of AOC4P expression in poorly metastatic EOC cell lines remarkably facilitated cell migration/invasion while the overexpression of AOC4P in highly metastatic EOC cell lines reduced the metastatic ability of these cells in vitro. Consistently, the anti-metastatic role of AOC4P in vivo was also verified by bioluminescence imaging and tumour dissection. Mechanistically, the anti-metastatic effect of AOC4P in EOC was partially mediated by the EMT process accompanied by the alterations in MMP9 and COL1A2 expression.
Conclusion:
These data highlight that AOC4P plays a critical role in EOC invasion/metastasis and could function as a novel and effective target for the lncRNA-based anti-metastatic clinical management of EOC.
Insights
Long non-coding RNA AOC4P acts as a tumor suppressor in epithelial ovarian cancer (EOC) by inhibiting metastasis. Decreased AOC4P expression correlates with advanced EOC stages and promotes epithelial-mesenchymal transition (EMT), suggesting its potential as an anti-metastatic therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of long non-coding RNAs (lncRNAs) in epithelial ovarian cancer (EOC) metastasis, particularly their involvement in the epithelial-mesenchymal transition (EMT), is not well understood.
- Identifying specific lncRNAs and their mechanisms in EOC metastasis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the function and mechanism of the lncRNA AOC4P in the metastasis of epithelial ovarian cancer (EOC).
- To determine if AOC4P plays a role in the epithelial-mesenchymal transition (EMT) process within EOC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) was used to assess AOC4P gene expression.
- Transwell and scratch assays were employed to evaluate cell migration and invasion.
- In vivo metastatic activity was assessed using an intraperitoneal metastasis model.
- Downstream gene expression related to EMT was analyzed using an RT-PCR array and validated by qRT-PCR and Western blot.
Main Results:
- AOC4P expression was found to be decreased in EOC tissues and cell lines, with lower expression correlating positively with advanced FIGO stage and lymph node metastasis.
- Knockdown of AOC4P enhanced EOC cell migration and invasion, while its overexpression reduced metastatic ability in vitro.
- AOC4P demonstrated an anti-metastatic role in vivo, partially mediated by the EMT process and alterations in MMP9 and COL1A2 expression.
Conclusions:
- AOC4P plays a significant role in inhibiting EOC invasion and metastasis.
- AOC4P has the potential to serve as a novel therapeutic target for lncRNA-based anti-metastatic strategies in EOC management.
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