RUNX3 regulates renal cell carcinoma metastasis via targeting miR-6780a-5p/E-cadherin/EMT signaling axis

Abstract

// Feifei Chen 1, * , Xin Liu 1, 5, * , Qian Cheng 2 , Shudong Zhu 4 , Jin Bai 1 and Junnian Zheng 2, 3 1 Jiangsu Cancer Biotherapy Institute, Xuzhou Medical College, Xuzhou, Jiangsu, P.R. China 2 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China 3 Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China 4 State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China 5 Department of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China * These authors have contributed equally to this work Correspondence to: Junnian Zheng, email: jnzheng@xzmc.edu.cn Jin Bai, email: bj@xzmc.edu.cn Shudong Zhu, email: shudongzhu@csu.edu.cn Keywords: RUNX3; renal cell carcinoma; tumor suppressor; E-cadherin; miR-6780a-5p Received: November 26, 2015     Accepted: July 06, 2016      Published: November 08, 2017 ABSTRACT Runt-related transcription factor 3 (RUNX3) is a tumor suppressor in many human solid tumors. In this study, renal cell carcinoma (RCC) microarray analysis showed that the level of RUNX3 expression was lower in RCC tissue than in adjacent normal renal tissues, and was correlated with depth of invasion (pT stage) ( P <0.001) and Tumor Node Metastasis (TNM) stage ( P <0.001). RUNX3 expression was negatively correlated with poor 5-year overall and disease-free patient survival. RUNX3 suppressed RCC metastasis and invasion and increased levels of E-cadherin, an important marker of epithelial-mesenchymal transition, in vitro and in vivo . RUNX3 also inhibited microRNA-6780a-5p, which directly targeted the E-cadherin 3’untranslated region and decreased its expression. We confirmed that miR-6780a-5p mimics abrogated RUNX3-mediated E-cadherin upregulation and RCC metastasis/invasion inhibition. Thus, RUNX3 targeted the miR-6780a-5p/E-cadherin/EMT signaling axis to suppress renal carcinoma cell migration and invasion. This pathway illustrates a new RUNX3 function and provides potential targets for the treatment of RUNX3 mutant and loss-of-function RCC tumors. RUNX3 may also act as an effective prognostic indicator in RCC.