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Updated: Jul 13, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B
Pornima Phatak1,2, Mohan E Tulapurkar3, Whitney M Burrows4
1Birmingham Veterans Affairs Health Care System, Birmingham, AL 35233, USA.
Abstract:
MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B.
Insights
MicroRNA (miR)-199a-5p acts as a tumor suppressor in esophageal cancer by reducing Jun-B expression. This microRNA targets Jun-B mRNA, inhibiting esophageal cancer cell proliferation and AP-1 activity.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNA (miR)-199a-5p exhibits tumor suppressor roles in various cancers, but its function in esophageal cancer remains unclear.
- Esophageal cancer is a significant global health concern, necessitating research into novel therapeutic targets and molecular mechanisms.
- The AP1 transcription factor, particularly its component Jun-B, is implicated in cancer progression and may be regulated by microRNAs.
Purpose of the Study:
- To investigate the role of miR-199a-5p in esophageal cancer.
- To elucidate the interaction between miR-199a-5p and Jun-B in esophageal cancer cells.
- To determine the functional consequences of this interaction on cancer cell proliferation and AP-1 activity.
Main Methods:
- Quantitative real-time PCR to assess miR-199a-5p and Jun-B expression levels in esophageal cancer tissues and cell lines.
- Western blotting to evaluate Jun-B protein expression.
- Biotinylated RNA-pull down assays and luciferase reporter assays to confirm direct interaction between miR-199a-5p and Jun-B mRNA.
- Cell proliferation assays and AP-1 promoter activity analysis following miR-199a-5p overexpression or Jun-B silencing.
Main Results:
- miR-199a-5p levels were significantly reduced in esophageal cancer specimens and cell lines, while Jun-B expression was elevated.
- Overexpression of miR-199a-5p led to decreased Jun-B mRNA stability, protein expression, and AP-1 promoter activity.
- A direct binding interaction between miR-199a-5p and Jun-B mRNA was experimentally validated.
- Both miR-199a-5p overexpression and Jun-B silencing significantly inhibited esophageal cancer cell proliferation.
Conclusions:
- miR-199a-5p functions as a tumor suppressor in esophageal cancer.
- The tumor-suppressive role of miR-199a-5p is mediated, in part, by the repression of Jun-B.
- Targeting the miR-199a-5p/Jun-B axis may offer a potential therapeutic strategy for esophageal cancer.
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