Related Experiment Video
Updated: Apr 11, 2026
A Cancer Cell Spheroid Assay to Assess Invasion in a 3D Setting
Published on: November 20, 2015
SRF-miR‑29b-MMP2 axis inhibits NSCLC invasion and metastasis
Hong-Yan Wang1, Yong-Sheng Tu2, Jie Long1
1Department of Pathology, School of Basic Sciences, Guangzhou Medical University, Guangdong 510180, P.R. China.
Abstract:
MicroRNAs play key roles in tumour metastasis. miR‑29b was previously reported to act as a tumour suppressor or an oncogene in diverse cancers. However, its accurate function and mechanism in metastasis of no-small cell lung cancer (NSCLC) are not well known. In this study, we describe the function of miR‑29b in NSCLC metastasis and its regulatory mechanisms. We found that miR‑29b is downregulated in high-metastatic NSCLC cells and low-expression of miR‑29b in primary NSCLC tissue was correlated with lymph node metastasis. Both gain- and loss-of-function study indicated overexpression of miR‑29b could suppress migration and invasion abilities of high-metastatic NSCLC cells, while downregulation of miR‑29b expression promoted migration and invasion of low-metastatic NSCLC cells in vitro. Moreover, introduction of miR‑29b inhibited high‑metastatic NSCLC cells, in vivo, metastasis to liver and lungs. Mechanistically, miR‑29b, induced by the transcription factor SRF, posttranscriptionally downregulates MMP2 expression by directly targeting its 3'-untranslated regions. These findings indicate a new regulatory mode, whereby miR‑29b, which is inhibited by its upstream transcription factor SRF, was able to promote its direct target MMP2 leading to NSCLC invasion and metastasis.
Insights
MicroRNA-29b (miR-29b) suppresses metastasis in non-small cell lung cancer (NSCLC). Its downregulation promotes cancer cell invasion and spread, while its restoration inhibits metastasis by targeting MMP2.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs are crucial regulators of tumor metastasis.
- The role of miR-29b in non-small cell lung cancer (NSCLC) metastasis is not fully understood.
- miR-29b has shown contradictory functions as a tumor suppressor or oncogene in various cancers.
Purpose of the Study:
- To elucidate the function and regulatory mechanisms of miR-29b in NSCLC metastasis.
- To investigate the correlation between miR-29b expression and lymph node metastasis in NSCLC patients.
- To identify the molecular targets and pathways regulated by miR-29b in NSCLC.
Main Methods:
- Analysis of miR-29b expression in NSCLC cell lines with varying metastatic potential.
- In vitro gain- and loss-of-function studies to assess cell migration and invasion.
- In vivo metastasis assays in animal models.
- Luciferase reporter assays to validate direct targeting of MMP2 by miR-29b.
Main Results:
- miR-29b expression is downregulated in highly metastatic NSCLC cells.
- Low miR-29b expression in primary tumors correlates with lymph node metastasis.
- Overexpression of miR-29b suppresses NSCLC cell migration, invasion, and in vivo metastasis.
- miR-29b directly targets the 3'-untranslated region of MMP2, downregulating its expression.
- SRF acts as an upstream transcription factor that inhibits miR-29b.
Conclusions:
- miR-29b functions as a tumor suppressor in NSCLC metastasis.
- Downregulation of miR-29b, induced by SRF, promotes NSCLC cell invasion and metastasis by upregulating MMP2.
- miR-29b represents a potential therapeutic target for inhibiting NSCLC metastasis.
