MATN1-AS1 Promotes Tumour Metastasis and Sunitinib Resistance via E2F2 in Clear Cell Renal Cell Carcinoma
- J Cell Mol Med. 2025 Feb;29(4):e70428. doi: 10.1111/jcmm.70428.
- 1. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- 2. Anhui Provincal Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Anhui, China.
- 3. Department of Urology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- 4. Department of Urology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
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.