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Long non-coding RNA FOXO1 inhibits lung cancer cell growth through down-regulating PI3K/AKT signaling pathway
Xiaoqian Ding1, Qiang Wang1, Li Tong1
1Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.
Objectives:
Lung cancer is one of the most common malignant tumors, which seriously threatens the health and life of the people. Recently, a novel long non-coding RNA (lncRNA) termed lncFOXO1 was found and investigated in breast cancer. However, the effect of lncFOXO1 on lung cancer is still ambiguous. The current study aimed to uncover the functions of lncFOXO1 in lung cancer cell proliferation, metastasis and apoptosis.
Materials And Methods:
LncFOXO1 expression levels in lung cancer tissues or cells were detected using qRT-PCR. Then, overexpression and knockdown vectors of lncFOXO1 were transfected into A549 cells to investigate the effect of lncFOXO1 on cell proliferation, invasion, migration and apoptosis. These experiments were assessed using MTT, colony formation, transwell, flow cytometry and western blot assays, respectively. In vivo experiment was performed to examine the tumor weight using Xenograft tumor model assay. The important pathway of PI3K/AKT was finally examined using western blot.
Results:
The decreased expression level of lncFOXO1 was observed in lung cancer tissues and cells (A549, H460, HCC827 and H1299). Knockdown of lncFOXO1 significantly promoted A549 cells viability, colony formation and invasion. However, lncFOXO1 overexpression obviously reversed the results. Moreover, lncFOXO1 overexpression induced A549 cells apoptosis by regulating Bax, cleaved-caspase-3 and Bcl-2. In vivo experiment revealed that lncFOXO1 overexpression inhibited tumor weight. Furthermore, lncFOXO1 knockdown promoted colony formation and mediated Myc and Cyclin D1 expressions by regulating PI3K/AKT signaling pathway.
Conclusion:
LncFOXO1 inhibited lung cancer cell proliferation, metastasis, and induced apoptosis through down-regulating PI3K/AKT pathway.
Insights
Long non-coding RNA FOXO1 (lncFOXO1) acts as a tumor suppressor in lung cancer. Overexpression of lncFOXO1 inhibits lung cancer cell proliferation and metastasis by down-regulating the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Gene Expression
Background:
- Lung cancer is a leading cause of cancer-related mortality worldwide.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- The function of lncFOXO1 in lung cancer remains largely unexplored.
Purpose of the Study:
- To investigate the role of lncFOXO1 in lung cancer cell proliferation, metastasis, and apoptosis.
- To elucidate the underlying molecular mechanisms, including the PI3K/AKT signaling pathway.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess lncFOXO1 expression.
- Cell transfection with lncFOXO1 overexpression and knockdown vectors in A549 cells.
- Assays included MTT, colony formation, Transwell, flow cytometry, and Western blot.
- In vivo studies using a Xenograft tumor model.
Main Results:
- lncFOXO1 expression was decreased in lung cancer tissues and cell lines.
- lncFOXO1 knockdown promoted cell viability, colony formation, and invasion.
- lncFOXO1 overexpression inhibited tumor growth and induced apoptosis.
- lncFOXO1 regulated the PI3K/AKT pathway, affecting Myc and Cyclin D1 expression.
Conclusions:
- lncFOXO1 functions as a tumor suppressor in lung cancer.
- lncFOXO1 inhibits proliferation and metastasis while promoting apoptosis.
- The tumor-suppressive effects are mediated through the down-regulation of the PI3K/AKT pathway.
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