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Published on: August 27, 2019
lncRNA DLEU1 contributes to tumorigenesis and development of endometrial carcinoma by targeting mTOR
Yuping Du1, Lili Wang2, Shuo Chen2
1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Key Laboratory for Major Obstetric Diseases of Guangdong Province, and Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou, China.
Abstract:
lncRNA DLEU1 as a non-coding gene, involves in the occurrence and development of multiple tumors. However, there is no related report in endometrial carcinoma. In order to focus on the role and mechanism of lncRNA DLEU1 in endometrial carcinoma, we used qRT-PCR to detect the expression of lncRNA DLEU1 and found that lncRNA DLEU1 was highly expressed in endometrial carcinoma compared to normal endometrium. Moreover, compared to Ishikawa and KLE, lncRNA DLEU1 was higher in HEC-1B. In addition, up-regulation of lncRNA DLEU1 promoted cell viability, migration, invasion, and reduced the proportion of apoptosis. Otherwise, down-regulation of lncRNA DLEU1 produced opposite results. Xenograft nude mice model assay showed that lncRNA DLEU1 can promote tumorigenesis in vivo. RiP confirmed that lncRNA DLEU1 could bind to mTOR. The rescue experiments revealed that silence of mTOR after up-regulation of lncRNA DLEU1 resulted in decrease of cell viability, migration, and invasion and increase of apoptosis. The expression changes of PI3K, AKT1, p70S6K, rpS6, GSK3β, STAT3, and Bcl-xl were consistent with lncRNA DLEU1 and mTOR in Western blot. Thus, we suggest that lncRNA DLEU1 combines with mTOR and then increases the expression of PI3K/AKT/mTOR pathway to promote endometrial carcinoma tumorigenesis and progression. The present discovery has probability to provide a biomarker and lay the foundation for targeted therapy of endometrial carcinoma.
Insights
Long non-coding RNA DLEU1 (lncRNA DLEU1) promotes endometrial carcinoma by activating the PI3K/AKT/mTOR pathway. This finding offers potential for new diagnostic biomarkers and targeted therapies for endometrial cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Expression
Background:
- Long non-coding RNAs (lncRNAs) are implicated in various cancers.
- The role of lncRNA DLEU1 in endometrial carcinoma (EC) remains unexplored.
- Understanding lncRNA DLEU1's function in EC is crucial for potential therapeutic strategies.
Purpose of the Study:
- To investigate the expression, function, and mechanism of lncRNA DLEU1 in endometrial carcinoma.
- To determine if lncRNA DLEU1 acts as a biomarker or therapeutic target in EC.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) for lncRNA DLEU1 expression analysis.
- Cell viability, migration, invasion, and apoptosis assays in EC cell lines.
- Xenograft nude mouse models for in vivo tumorigenesis assessment.
- RNA immunoprecipitation (RIP) and Western blot to identify molecular interactions and pathway activation.
Main Results:
- lncRNA DLEU1 was significantly upregulated in endometrial carcinoma tissues and cell lines.
- Overexpression of lncRNA DLEU1 enhanced EC cell proliferation, migration, and invasion while reducing apoptosis.
- lncRNA DLEU1 directly binds to mTOR, activating the PI3K/AKT/mTOR signaling pathway.
- lncRNA DLEU1 promoted tumor growth in vivo.
Conclusions:
- lncRNA DLEU1 plays a critical role in promoting endometrial carcinoma progression.
- The lncRNA DLEU1/mTOR/PI3K/AKT pathway is a key mechanism driving EC tumorigenesis.
- lncRNA DLEU1 represents a promising biomarker and therapeutic target for endometrial carcinoma.
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