MATN1‐AS1 Promotes Tumour Metastasis and Sunitinib Resistance via E2F2 in Clear Cell Renal Cell Carcinoma

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.