1. For the first time, the potential mechanisms underlying the critical role of miR-516a in bladder cancer metastasis is revealed. 2. MiR-516a promotes migration and invasion of human bladder cancer cells by targeting PHLPP2 and subsequently inhibiting SMURF1-mediated MMP9 protein degradation. 3. Based on the metastatic role of miR-516a in bladder cancer, our findings provide promising targets for bladder cancer therapy.
Extensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle–related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer.
Graphical abstract
Due to the lack of effective early diagnostic measures and treatment methods, bladder cancer has become a malignant tumor that seriously threatens people's lives and health. Here, we reported that LINC00162, a super-enhancer long noncoding RNA, was highly expressed in bladder cancer cells and tissues. And LINC00162 was negatively correlated with neighboring PTTG1IP expression. Knocking down LINC00162 expression can inhibit the proliferative activity of bladder cancer cells and the growth of transplanted tumors in vivo, while knocking down the expression of PTTG1IP could restore the proliferative activity of bladder cancer cells. In addition, both LINC00162 and PTTG1IP were found to be able to bind to THRAP3, a transcription-related protein. And THRAP3 can regulate PTTG1IP expression. Finally, we demonstrated a mechanism that LINC00162 could regulate PTTG1IP expression through binding THRAP3. This study provided a potential target molecule for clinical treatment of bladder cancer.
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