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Hsa_circ_0091074 regulates TAZ expression via microRNA‑1297 in triple negative breast cancer cells.

Int J Oncol. 2020 May;56(5):1314-1326. doi:10.3892/ijo.2020.5000. Epub 2020 Feb 25
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摘要


Triple negative breast cancer (TNBC) has the highest recurrence, metastasis and mortality rate of all breast cancer subtypes, due to its typically more aggressive characteristics and lack of effective targeted treatment options. The Hippo pathway is a signaling cascade composed of a group of conserved kinases, which serves an important role in almost all cancer types. Both circular RNAs (circRNAs) and microRNAs (miRNAs) are types of non‑coding RNAs, which influence cancer progression. CircRNAs have been demonstrated to serve as miRNA 'sponges', binding to miRNAs to inhibit their function. In the present study, it was revealed that circular RNA hsa_circ_0091074 binds miR‑1297, and that there is an inverse association between the expression levels of the two non‑coding RNAs in breast cells, indicating that hsa_circ_0091074 may serve as an endogenous 'sponge' for miR‑1297. Subsequently, the potential function and mechanism underlying the involvement of miR‑1297 in breast cancer was investigated via MTT, colony formation, wound healing and cell cycle assays. Increased miR‑1297 expression resulted in a decrease in the protein levels of critical Hippo pathway transcriptional mediator Transcriptional coactivator with PDZ‑binding motif (TAZ), which is a putative target of miR‑1297. This was confirmed using dual‑luciferase reporter assays, which revealed that miR‑1297 targets TAZ by binding its 3'‑untranslated region (3'UTR). The current results indicate that miR‑1297 serves as a suppressor of breast cancer cell proliferation and invasiveness, and that this can be partially reversed by hsa_circ_0091074, suggesting that the hsa_circ_0091074/miR‑1297/TAZ/TEAD4 axis may represent a potential therapeutic target for triple negative breast cancer in the future.

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原始数据


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