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Updated: May 26, 2025

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
MATN1-AS1 Promotes Tumour Metastasis and Sunitinib Resistance via E2F2 in Clear Cell Renal Cell Carcinoma
Haibing Xiao1,2, Mintian Fei1,2, Qili Xu1,2
1Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Abstract:
It has become increasingly recognised that MATN1-AS1 is involved in multiple tumour development. The role of MATN1-AS1 in clear cell renal cell carcinoma (ccRCC), however, is still largely unrecognised. This study investigated the molecular functions of MATN1-AS1 in promoting ccRCC metastasis and sunitinib resistance. MATN1-AS1 was found to be mainly located in the cytoplasm and was upregulated in ccRCC, and a positive association was seen between greater levels of MATN1-AS1 expression and worse clinical outcomes. Downregulating MATN1-AS1 significantly hindered cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). MATN1-AS1 promoted tumour growth and metastasis in vivo. Mechanismly, MATN1-AS1 targeted microRNA miR-214-5p, thereby upregulating E2F2 and promoting E2F2-mediated EMT. We discovered that MATN1-AS1 also promoted sunitinib resistance via E2F2 in vitro. Collectively, our research uncovered the protumor characteristics of MATN1-AS1 and suggested it as a therapeutic target for reverse sunitinib resistance in ccRCC.
Insights
The long non-coding RNA MATN1-AS1 promotes clear cell renal cell carcinoma (ccRCC) metastasis and sunitinib resistance by upregulating E2F2. Targeting MATN1-AS1 may offer a new strategy to overcome drug resistance in ccRCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly implicated in various cancers.
- The specific role of MATN1-AS1 in clear cell renal cell carcinoma (ccRCC) remains largely unexplored.
- Understanding lncRNA functions is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the molecular mechanisms of MATN1-AS1 in ccRCC progression.
- To determine the association between MATN1-AS1 and ccRCC metastasis and sunitinib resistance.
- To explore MATN1-AS1 as a potential therapeutic target for ccRCC.
Main Methods:
- Quantitative real-time PCR to assess MATN1-AS1 expression levels.
- Cell proliferation, migration, and invasion assays to evaluate cellular functions.
- In vivo tumor xenograft models to study tumor growth and metastasis.
- Western blotting and luciferase reporter assays to elucidate molecular pathways.
Main Results:
- MATN1-AS1 is upregulated in ccRCC tissues and associated with poor clinical outcomes.
- Downregulation of MATN1-AS1 inhibits ccRCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- MATN1-AS1 promotes ccRCC tumor growth and metastasis in vivo.
- MATN1-AS1 acts as a molecular sponge for miR-214-5p, leading to E2F2 upregulation and EMT promotion.
- MATN1-AS1 enhances sunitinib resistance in ccRCC cells via E2F2.
Conclusions:
- MATN1-AS1 exhibits significant protumorigenic functions in ccRCC.
- MATN1-AS1 promotes ccRCC metastasis and resistance to sunitinib treatment.
- MATN1-AS1 represents a potential therapeutic target for reversing sunitinib resistance in ccRCC.
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