Laboratorio de Investigação Médica 55 (LIM55), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil.
Faculdade de Medicina, Universidade Federal do Pará, Belém, PA, Brazil.
Mol Biol Rep. 2021 Dec;48(12):7947-7952. doi: 10.1007/s11033-021-06825-9. Epub 2021 Oct 27.
Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays. METHODS AND RESULTS: T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002).
Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA's role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.
膀胱癌是影响男性和女性的主要移行细胞癌，其发病率和死亡率都很高，因此有必要开发新的分子靶向治疗方法，利用 microRNAs。本研究旨在通过侵袭、迁移、凋亡和细胞周期测定，评估 T24 细胞系转染 miR-Let-7c 前体模拟物后的行为。
T24 细胞用 Let-7c 模拟物及其相应的对照物转染，并在 24 小时后进行评估。通过 qPCR 分析 miR-Let-7c 的表达水平。我们进行了划痕愈合、Matrigel 和流式细胞术、凋亡和细胞周期测定，以确定其对细胞过程的影响。转染 miR-Let-7c 的细胞显示出更高的凋亡率（p = 0.019），24 小时（p = 0.031）和 48 小时（p = 0.0006）迁移减少，侵袭潜能（p = 0.0007）和细胞增殖（p = 0.002）减少。
我们的结果表明，miR-Let-7c 可以作用于肌层浸润性尿路上皮癌细胞的致癌细胞过程的不同途径，抑制细胞增殖并增加细胞凋亡水平，从而限制其侵袭潜能。然而，应该进行进一步的研究，以更好地阐明这种 microRNA 在高级别尿路上皮癌中的作用，并揭示该 microRNA 可能存在的靶点，这些靶点与癌症的生存途径密切相关。
