Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, P.R. China.
Department of Clinical Laboratory, Chongqing University Cancer Hospital, Chongqing, P.R. China.
Carcinogenesis. 2022 Mar 24;43(2):150-159. doi: 10.1093/carcin/bgab124.
Breast cancer is the most common malignancy among women worldwide. Functional studies have demonstrated that miRNA dysregulation in many cases of cancer, in which miRNAs act as either oncogenes or tumor suppressor. Here we report that miR-345-3p is generally upregulated in breast cancer tissues and breast cancer cell lines. Overexpression and inhibition of miR-345-3p revealed its capacity in regulating proliferation and invasion of breast cancer cells. Further research identified protein phosphatase 2 catalytic subunit alpha (PPP2CA), a suppressor of AKT phosphorylation, as a candidate target of miR-345-3p. In vitro, miR-345-3p mimics promoted AKT phosphorylation by targeting its negative regulator, PPP2CA. Blocking miR-345-3p relieved its inhibition of PPP2CA, which attenuated PI3K-AKT signaling pathway. In vivo, inhibiting miR-345-3p by miR-345-3p-inhibition lentivirus suppressed tumor growth and invasiveness in mice. Together, the miR-345-3p/PPP2CA signaling axis exhibits tumor-promoting functions by regulating proliferation and invasion of breast cancer cells. These data provide a clue to novel therapeutic approaches for breast cancer.
乳腺癌是全球女性中最常见的恶性肿瘤。功能研究表明，在许多癌症病例中，miRNA 失调，miRNA 可以作为癌基因或肿瘤抑制因子发挥作用。在这里，我们报告 miR-345-3p 在乳腺癌组织和乳腺癌细胞系中普遍上调。miR-345-3p 的过表达和抑制揭示了其调节乳腺癌细胞增殖和侵袭的能力。进一步的研究确定蛋白磷酸酶 2 催化亚基 α（PPP2CA）是 AKT 磷酸化的抑制剂，是 miR-345-3p 的候选靶标。在体外，miR-345-3p 模拟物通过靶向其负调节剂 PPP2CA 促进 AKT 磷酸化。阻断 miR-345-3p 减轻其对 PPP2CA 的抑制，从而减弱 PI3K-AKT 信号通路。在体内，通过 miR-345-3p 抑制慢病毒抑制 miR-345-3p 抑制了小鼠肿瘤的生长和侵袭。总之，miR-345-3p/PPP2CA 信号轴通过调节乳腺癌细胞的增殖和侵袭发挥促进肿瘤的功能。这些数据为乳腺癌的新治疗方法提供了线索。
