MATN1-AS1通过E2F2促进透明细胞肾细胞癌的肿瘤转移和舒尼替尼耐药。

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

作者信息

Xiao Haibing, Fei Mintian, Xu Qili, Gao Yu, Feng Rui, Liang Chaozhao, Wang Baojun, Li Haolin

机构信息

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Anhui Provincal Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Anhui, China.

出版信息

J Cell Mol Med. 2025 Feb;29(4):e70428. doi: 10.1111/jcmm.70428.

DOI:10.1111/jcmm.70428

PMID:39999286

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11855375/

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.

摘要

越来越多的人认识到MATN1 - AS1参与多种肿瘤的发生发展。然而，MATN1 - AS1在透明细胞肾细胞癌（ccRCC）中的作用仍在很大程度上未被认识。本研究探讨了MATN1 - AS1在促进ccRCC转移和舒尼替尼耐药中的分子功能。研究发现MATN1 - AS1主要位于细胞质中，且在ccRCC中上调，MATN1 - AS1表达水平越高与临床预后越差呈正相关。下调MATN1 - AS1显著阻碍细胞增殖、迁移、侵袭及上皮 - 间质转化（EMT）。MATN1 - AS1在体内促进肿瘤生长和转移。机制上，MATN1 - AS1靶向微小RNA miR - 214 - 5p，从而上调E2F2并促进E2F2介导的EMT。我们还发现MATN1 - AS1在体外也通过E2F2促进舒尼替尼耐药。总之，我们的研究揭示了MATN1 - AS1的促肿瘤特性，并提示其可作为逆转ccRCC中舒尼替尼耐药的治疗靶点。