ZNF139/circZNF139 promotes cell proliferation, migration and invasion via activation of PI3K/AKT pathway in bladder cancer

Abstract

Existing reports identify the involved roles of <i>ZNF139</i> and its one circular RNA (circRNA), circZNF139, in the progression of various tumors. However, their relevance and function role in bladder cancer (BC) remain largely unexplored. Herein, we aimed to reconnoiter the role and potential mechanism of <i>ZNF139</i> and <i>circZNF139</i> in the progression of BC. Firstly, bioinformatics analyses indicated <i>ZNF139</i> was upregulated in BC tissues and correlated with disease-free survival of BC patients. The subcellular localization and structural analyses of <i>ZNF139</i> conveyed the possibility of <i>ZNF139</i> functioning as a transcription factor. Secondly, <i>circZNF139</i> was validated by bioinformatics analyses and RNase R tests. <i>ZNF139</i> and <i>circZNF139</i> were both significantly upregulated in BC cell lines. Functionally, <i>ZNF139</i>/<i>circZNF139</i> had facilitated effects on the proliferative, clonal, migratory, and invasive potential of BC cells. Mechanistically, GO, KEGG pathway analyses and western blot assays altogether unveiled <i>ZNF139</i>/<i>circZNF139</i> activated PI3K/AKT pathway in BC cells, supported by the alteration of AKT at phosphorylation level and PI3K at the protein level. Collectively, this work reveals <i>ZNF139</i> and <i>circZNF139</i> cooperate closely with each other to promote cell proliferation, migration and invasion via activation of PI3K/AKT pathway in BC.