Related Experiment Video
Updated: Mar 24, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR-99a regulates ROS-mediated invasion and migration of lung adenocarcinoma cells by targeting NOX4
Mei Sun1, Shunming Hong2, Wenhan Li2
1Department of Radiation Oncology, Tianjin Huan Hu Hospital, Tianjin 300060, P.R. China.
Abstract:
miR-99a is frequently downregulated in various types of human malignancies including lung adenocarcinoma. Recent studies have reported that miR-99a regulates cell growth and cell cycle progression by targeting mTOR, AKT1 and FGFR3. However, the underlying mechanisms involved in the modulation of invasion and migration by miR-99a remain elusive. In this study, we analyzed the relationship between the expression of miR-99a and clinical stage or metastasis in 90 matched lung adenocarcinoma and adjacent non-tumor lung tissues. Downregulation of miR-99a was significantly associated with advanced stage and tumor metastasis in lung adenocarcinoma patients, and it was found to be a poor prognostic factor in lung adenocarcinoma. Furthermore, functional experiments found that overexpression of miR-99a inhibited the proliferation, migration and invasion of lung adenocarcinoma A549 and Calu3 cells in vitro. We then identified NOX4 as a target gene of miR-99a and NOX4 mediated the inhibition of invasion and migration of lung adenocarcinoma cells by miR-99a. By targeting NOX4-mediated ROS production, miR-99a regulated the invasion and migration of lung adenocarcinoma cells. Moreover, overexpression of miR-99a significantly inhibited tumor growth in vivo. Immunohistochemical staining analysis of the mouse tumor tissues revealed that NOX4 levels were downregulated in the miR-99a treatment group, confirming the in vitro data of NOX4 as a direct target gene of miR-99a. Taken together, these data indicate for the first time that miR-99a directly regulates the invasion and migration in lung adenocarcinoma by targeting NOX4 and that overexpression of miR-99a may become a therapeutic strategy for lung adenocarcinoma.
Insights
MicroRNA-99a (miR-99a) downregulation is linked to advanced lung adenocarcinoma. This study shows miR-99a inhibits cancer cell invasion and migration by targeting NOX4, suggesting miR-99a as a potential therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA-99a (miR-99a) is often downregulated in human cancers, including lung adenocarcinoma.
- Previous research linked miR-99a to cell growth and cycle regulation via mTOR, AKT1, and FGFR3.
- The role of miR-99a in modulating cancer cell invasion and migration was not fully understood.
Purpose of the Study:
- To investigate the relationship between miR-99a expression and clinical features of lung adenocarcinoma.
- To elucidate the mechanisms by which miR-99a affects lung adenocarcinoma cell invasion and migration.
- To explore the therapeutic potential of miR-99a in lung adenocarcinoma.
Main Methods:
- Analysis of miR-99a expression in 90 lung adenocarcinoma tissues and matched adjacent non-tumor tissues.
- In vitro functional assays (proliferation, migration, invasion) using lung adenocarcinoma cell lines (A549, Calu3) with miR-99a overexpression.
- Identification of NOX4 as a direct target of miR-99a and assessment of its role in miR-99a-mediated effects.
- In vivo tumor growth inhibition studies in mice with subsequent immunohistochemical analysis of NOX4 levels.
Main Results:
- Downregulation of miR-99a significantly correlated with advanced clinical stage and metastasis in lung adenocarcinoma patients.
- Overexpression of miR-99a suppressed proliferation, migration, and invasion of lung adenocarcinoma cells in vitro.
- NOX4 was identified as a direct target of miR-99a, and its targeting mediated the inhibition of cell invasion and migration via ROS production.
- In vivo studies confirmed that miR-99a overexpression inhibited tumor growth and downregulated NOX4 levels.
Conclusions:
- miR-99a directly regulates invasion and migration in lung adenocarcinoma by targeting NOX4.
- Targeting NOX4-mediated ROS production is a key mechanism for miR-99a's anti-cancer effects.
- Overexpression of miR-99a demonstrates therapeutic potential for lung adenocarcinoma treatment.
More Related Videos
Related Concept Videos
01:22MicroRNAs
02:23Abnormal Proliferation