QKI‐6 inhibits bladder cancer malignant behaviours through down‐regulating E2F3 and NF‐κB signalling

作者：Fei Shi, Zheng Deng, Zheng Zhou, Chenyi Jiang, Ruizhe Zhao, Feng Sun, Di Cui, Xiao‐Yu Bei, Boyu Yang, Qian Sun, Xing‐Jie Wang, Qi Wu, Shujie Xia, Bangmin Han · 发表于：Journal of Cellular and Molecular Medicine · 年份：2019 · DOI：10.1111/jcmm.14481 · 被引用次数：30 · 研究领域：RNA Research and Splicing、Genetic factors in colorectal cancer、Cancer-related molecular mechanisms research

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel mult...