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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-486-5p specifically suppresses SAPCD2 expression, which attenuates the aggressive phenotypes of lung
1Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, China. ghuasd1990@163.com.
Background:
MiR-486-5p expression is restrained in lung adenocarcinoma (LUAD). However, much less has been understood on its role in LUAD. We aimed to explore the biofunctions of miR-486-5p in LUAD.
Methods:
A differential expression analysis based on The Cancer Genome Atlas-LUAD dataset was done to screen the differently expressed miRNAs and mRNAs. MiR-486-5p and SAPCD2 mRNA expression was analyzed by qRT-PCR, and protein level of SAPCD2 was assayed by western blot. Upregulation and downregulation of miR-486-5p or SAPCD2 were achieved by cell transfection. For cell function assays, the proliferation of cancer cells was examined by MTT assay. Cell apoptosis was assessed by flow cytometry and microscopy. Transwell assay was applied to evaluate cell migration and invasion. A dual-luciferase detection was employed to determine the miRNA-mRNA targeting relationship.
Results:
MiR-486-5p expression was notably reduced in LUAD tissue and cell lines. Upregulating miR-486-5p restrained the anti-apoptotic and proliferative abilities, as well as cell migratory and invasive phenotypes in LUAD cells. SAPCD2 was determined as one target of miR-486-5p. Also, SAPCD2 forced expression was able to attenuate the inhibitory impacts of miR-486-5p on the malignant phenotypes of LUAD cells.
Conclusion:
MiR-486-5p suppressed cell malignant progression in LUAD by targeting SAPCD2, suggesting that the two may be targets for LUAD treatment.
Insights
MicroRNA-486-5p (miR-486-5p) is downregulated in lung adenocarcinoma (LUAD). Restoring miR-486-5p suppresses LUAD cell proliferation, apoptosis, migration, and invasion by targeting SAPCD2.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-486-5p (miR-486-5p) expression is significantly reduced in lung adenocarcinoma (LUAD).
- The precise role and biological functions of miR-486-5p in LUAD remain largely unexplored.
Purpose of the Study:
- To investigate the biofunctions of miR-486-5p in lung adenocarcinoma.
- To elucidate the molecular mechanisms underlying miR-486-5p's role in LUAD progression.
Main Methods:
- Differential gene expression analysis using The Cancer Genome Atlas (TCGA)-LUAD dataset.
- Quantitative real-time PCR (qRT-PCR) and Western blot to analyze miR-486-5p and SAPCD2 expression.
- In vitro functional assays including MTT, flow cytometry, Transwell assays, and dual-luciferase reporter assays to assess cell proliferation, apoptosis, migration, invasion, and miRNA-mRNA targeting.
Main Results:
- MiR-486-5p expression was found to be significantly downregulated in LUAD tissues and cell lines.
- Overexpression of miR-486-5p inhibited proliferation, anti-apoptotic tendencies, migration, and invasion of LUAD cells.
- SAPCD2 was identified as a direct target of miR-486-5p, and its forced expression could counteract the suppressive effects of miR-486-5p on LUAD cell malignant phenotypes.
Conclusions:
- MiR-486-5p acts as a tumor suppressor in LUAD by inhibiting malignant cell progression through targeting SAPCD2.
- MiR-486-5p and SAPCD2 represent potential therapeutic targets for lung adenocarcinoma treatment.

