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  • Title: CircRNA hsa_circ_0014130 function as a miR-132-3p sponge for playing oncogenic roles in bladder cancer via upregulating KCNJ12 expression.
    Author: Li G, Guo BY, Wang HD, Lin GT, Lan TJ, Ying H, Xu J.
    Journal: Cell Biol Toxicol; 2022 Dec; 38(6):1079-1096. PubMed ID: 34755307.
    Abstract:
    The modern categories of endogenous non-coding RNAs, namely circular RNAs (circRNAs), involved within the carcinogenesis and progression of various human cancers. The fundamental aim of the current investigation was the evaluation of the hsa_circ_0014130 expressions, their biological functions, and potential regulatory network in bladder cancer. The level of expression for hsa_circ_0014130 was evaluated by qRT-PCR, and its relationships to clinicopathological features and survival outcomes of cases experiencing cancer of the bladder were scrutinized. The impact of hsa_circ_0014130 expressions on biological attitudes of bladder cancer cells in vitro was investigated. The interactions between hsa_circ_0014130 and microRNA (miRNA) sponge, miRNA, and its direct targets were determined by RNA pull-down as well as luciferase reporter gene assay. The correlations of their expression were determined by Pearson's correlation analysis. Rescue experiments were carried out to identify the biological roles of the regulation network. The expressions of hsa_circ_0014130 were markedly ameliorated in bladder cancer samples and linked with aggressive characteristics and unfavorable survival. Ectopic expression of hsa_circ_0014130 clearly enhanced the differentiation, proliferative, migratory, invasive potential of the cell in bladder cancer, and the development of tumor xenograft in vivo, while malignant biological behaviors were inhibited by hsa_circ_0014130 knockdown. The expression of hsa_circ_0014130 was tied to miR-132-3p in a negative manner with the cells and tissues of bladder cancer. hsa_circ_0014130 function as a competitive endogenous RNA for miR-132-3p to play oncogenic roles in bladder cancer cells. On the other hand, KCNJ12 was a straightforward target of miR-132-3p at the downstream, and the expressions of KCNJ12 were inversely related to that of miR-132-3p. Furthermore, a significantly positive correlation was found between hsa_circ_0014130 and KCNJ12 mRNA expression. More importantly, the oncogenic impact of hsa_circ_0014130 on bladder cancer cells was partly suppressed by ectopic expression of miR-132-3p or KCNJ12 knockdown. The underlined data revealed that hsa_circ_0014130 exerted its biological roles by regulating miR-132-3p/KCNJ12 expression. Further research revealed hsa_circ_0014130/miR-132-3p/KCNJ12 axis has participated in the Epithelial-mesenchymal transition (EMT) progress and GSK3β/AKT signaling pathway. hsa_circ_0014130 works as a sponge of miR-132-3p to advance the oncogenesis and metastasis of bladder cancer by regulation of the KCNJ12 expression. These achievements might ameliorate the comprehension of tumor pathogenesis and provide novel therapeutic targets for cancer of the bladder.
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