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Published on: March 30, 2019
Long Noncoding RNA LINC01554 Inhibits the Progression of NSCLC Progression by Functioning as a ceRNA for miR-1267 and
Zizong Wang1, Bin Yang2, Jin Zhang3
1Department of Thoracic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
Objectives:
This study focused on the biological functions and mechanisms of action of LINC01554 in nonsmall cell lung cancer (NSCLC).
Methods:
The expression and prognostic values of LINC01554 in NSCLC were evaluated using The Cancer Genome Atlas datasets. MTT, colony formation, wound healing, transwell, and in vivo assays were performed to investigate the role of LINC01554 in NSCLC. The related protein expression levels were measured via western blotting. Bioinformatic analysis was conducted to predict targeted genes. The relationship between LINC01554, microRNA- (miR-) 1267, miR-1267, and inhibitor of growth family member 3 (ING3) was analysed via a dual-luciferase reporter assay.
Results:
LINC01554 expression was downregulated in NSCLC and associated with NSCLC prognosis. LINC01554 overexpression suppressed NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatic and dual-luciferase reporter assays demonstrated that LINC01554 expression directly targeted miR-1267 expression, which in turn directly acted on ING3. An miR-1267 mimic significantly reduced ING3 expression, whereas an miR-1267 inhibitor observably elevated its expression. LINC01554 overexpression increased ING3 expression, whereas this effect was counteracted by the miR-1267 mimic. LINC01554 overexpression also significantly suppressed the expression of phosphorylated protein kinase B (Akt) and phosphorylated mammalian target of rapamycin (mTOR) expression; this effect was abrogated by the miR-1267 mimic. Mechanistically, LINC01554 overexpression repressed the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells through the regulation of the miR-1267/ING3 axis via regulation of the Akt/mTOR signalling pathway.
Conclusions:
We provide the first evidence of the involvement of the LINC01554/miR-1267 axis in NSCLC proliferation and metastasis through the ING3Akt/mTOR pathway. Thus, LINC01554 may serve as a novel therapeutic target for NSCLC.
Insights
LINC01554, a long non-coding RNA, suppresses non-small cell lung cancer (NSCLC) growth and metastasis by targeting miR-1267 and the ING3/Akt/mTOR pathway. This finding highlights LINC01554 as a potential therapeutic target for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide.
- Understanding the molecular mechanisms driving NSCLC progression is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the biological functions and mechanisms of action of the long non-coding RNA LINC01554 in non-small cell lung cancer (NSCLC).
- To evaluate the prognostic value of LINC01554 in NSCLC patients.
Main Methods:
- Analysis of LINC01554 expression and prognostic value in NSCLC using The Cancer Genome Atlas (TCGA) datasets.
- In vitro and in vivo assays (MTT, colony formation, wound healing, transwell, in vivo assays) to assess the role of LINC01554 in NSCLC.
- Dual-luciferase reporter assays to elucidate the regulatory relationship between LINC01554, miR-1267, and ING3, and western blotting to measure protein expression.
Main Results:
- LINC01554 expression was found to be downregulated in NSCLC and correlated with poorer prognosis.
- Overexpression of LINC01554 inhibited NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- LINC01554 directly targets miR-1267, which in turn targets ING3. This axis regulates the Akt/mTOR signaling pathway, suppressing tumor growth and metastasis.
Conclusions:
- This study provides the first evidence for the involvement of the LINC01554/miR-1267/ING3 axis in regulating NSCLC proliferation and metastasis via the Akt/mTOR pathway.
- LINC01554 demonstrates potential as a novel therapeutic target for NSCLC treatment.
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