microRNA-1298 inhibits the malignant behaviors of breast cancer cells via targeting ADAM9.
microRNA-1298 inhibits the malignant behaviors of breast cancer cells via targeting ADAM9.
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DOI：
10.1042/bsr20201215
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发表时间：
2020-12-23
影响因子：
4
通讯作者：
Xue X
中科院分区：
文献类型：
--
作者：
Chen W;Lu Q;Li S;Zhang X;Xue X
microRNA（miRNAs）通过靶向癌基因或肿瘤抑制因子来调控人类恶性肿瘤的进展，这是12个有希望的癌症治疗靶点。越来越多的证据表明miR-1298在肿瘤中的异常表达和抑瘤作用，但miR-1298在乳腺癌中的调控机制尚不清楚。在此，我们的发现表明miR-1298在BC组织和细胞系中下调。miR-1298的低水平与BC患者的晚期进展显著相关。实验研究表明，miR-1298过表达可抑制BC细胞增殖，诱导细胞凋亡和细胞周期阻滞。体内异种移植小鼠模型显示，高表达的miR-1298显著降低肿瘤的生长和转移。进一步的机制分析表明，miR-1298与去整合素和金属蛋白酶9结构域（ADAM 9）的3′-非翻译区（UTR）结合，抑制了ADAM 9在BC细胞中的表达。ADAM 9在BC组织中过表达，并与miR-1298呈负相关。ADAM 9下调可诱导BC细胞凋亡和细胞周期阻滞。此外，通过瞬时转染编码ADAM 9全编码序列的载体异位表达ADAM 9可减弱miR-1298对BC细胞增殖和细胞周期进程的抑制作用。综上所述，miR-1298通过直接抑制ADAM 9的表达，对BC细胞表型的调节起抑制作用，提示miR-1298在BC的治疗中具有潜在的应用价值。
MicroRNAs (miRNAs) regulate the progression of human malignancy by targeting oncogenes or tumor suppressors, which are 12 promising targets for cancer treatment. Increasing evidence has suggested the aberrant expression and tumor-suppressive function of miR-1298 in cancers, however, the regulatory mechanism of miR-1298 in breast cancer (BC) remains unclear. Here, our findings showed that miR-1298 was down-regulated in BC tissues and cell lines. Lower level of miR-1298 was significantly correlated with the advanced progression of BC patients. Experimental study showed that overexpression of miR-1298 inhibited the proliferation, induced apoptosis and cell cycle arrest in BC cells. The in vivo xenograft mice model showed that highly expressed miR-1298 significantly reduced the tumor growth and metastasis. Further mechanism analysis revealed that miR-1298 bound the 3′-untranslated region (UTR) of a disintegrin and metalloproteinase 9 domain (ADAM9) and suppressed the expression of ADAM9 in BC cells. ADAM9 was overexpressed in BC tissues and inversely correlated with miR-1298. Down-regulation of ADAM9 induced apoptosis and cell cycle arrest of BC cells. Moreover, ectopic expression of ADAM9 by transiently transfecting with vector encoding the full coding sequence of ADAM9 attenuated the inhibitory effects of miR-1298 on the proliferation and cell cycle progression of BC cells. Collectively, our results illustrated that miR-1298 played a suppressive role in regulating the phenotype of BC cells through directly repressing ADAM9, suggesting the potential application of miR-1298 in the therapy of BC.