Department of Breast Disease, Linyi Central Hospital, Linyi, Shandong 276499, P.R. China.
Department of Emergency Surgery, Linyi Central Hospital, Linyi, Shandong 276499, P.R. China.
Mol Med Rep. 2019 Mar;19(3):2180-2188. doi: 10.3892/mmr.2019.9889. Epub 2019 Jan 23.
MicroRNA‑233‑3p (miR‑223‑3p) is considered an important cancer‑associated marker. The NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome represents a novel potential target for the treatment of breast cancer. Therefore, it was hypothesized that miR‑223‑3p may affect tumor growth and immunosuppression in breast cancer by inhibiting the NLRP3 inflammasome. In the present study, an increased expression level of NLRP3 was detected in three breast cancer cell lines compared with normal mammary epithelial cells (HMEC). Suppressing the expression of NLRP3 in MCF‑7 cell lines increased the apoptotic rate of breast cancer cells and reduced the proliferative capacity. NLRP3 was identified to be a direct target of miR‑233‑3p using a luciferase assay. In addition, miR‑233‑3p mimics inhibited the NLRP3‑dependent processes in cancer cells by suppressing the NLRP3 expression level and the protein expression levels of its downstream factors, including PYD and CARD domain containing protein, interleukin‑1β and interleukin‑18. In vivo experiments demonstrated the suppressive effect of miR‑233‑3p in tumor growth and immunosuppression. Collectively these findings suggested that the inactivation of the NLRP3 inflammasome driven by miR‑223‑3p reduced the growth and immunosuppression of breast cancer in vitro and in vivo, and may represent a novel therapeutic strategy in treating breast cancer.
miR-233-3p（miR-223-3p）被认为是一种重要的癌症相关标志物。NACHT、LRR 和 PYD 结构域包含蛋白 3（NLRP3）炎性小体是治疗乳腺癌的一个新的潜在靶点。因此，本研究假设 miR-223-3p 可能通过抑制 NLRP3 炎性小体影响乳腺癌的肿瘤生长和免疫抑制。在本研究中，与正常乳腺上皮细胞（HMEC）相比，在三种乳腺癌细胞系中检测到 NLRP3 的表达水平升高。在 MCF-7 细胞系中抑制 NLRP3 的表达可增加乳腺癌细胞的凋亡率并降低增殖能力。通过荧光素酶检测证实 NLRP3 是 miR-233-3p 的直接靶标。此外，miR-233-3p 模拟物通过抑制 NLRP3 表达水平及其下游因子 PYD 和 CARD 结构域包含蛋白、白细胞介素-1β 和白细胞介素-18 的蛋白表达水平，抑制了 NLRP3 依赖性过程。体内实验表明 miR-233-3p 对肿瘤生长和免疫抑制具有抑制作用。综上所述，这些研究结果表明，miR-223-3p 驱动的 NLRP3 炎性小体失活减少了乳腺癌在体内和体外的生长和免疫抑制，可能代表了治疗乳腺癌的一种新的治疗策略。
