STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer.
STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer.
复制标题
STIM1 是 microRNA-185 的直接靶标，可促进肿瘤转移并与结直肠癌不良预后相关
作者：
Zhang Z;Liu X;Feng B;Liu N;Wu Q;Han Y;Nie Y;Wu K;Shi Y;Fan D
基质相互作用分子1（stromal interaction molecule 1，STIM 1）是一种内质网Ca 2+传感器，可触发钙库操纵的Ca 2+内流激活。然而，STIM 1在结直肠癌（CRC）的进展和转移中的作用尚未得到解决。在这项研究中，我们证实了STIM 1在高侵袭性CRC细胞系中的表达增加。STIM 1的表达增强在体外和体内促进CRC细胞转移，而用小干扰RNA沉默STIM 1导致转移减少。CRC细胞中STIM 1的异位表达可诱导上皮向间充质转化（EMT），而STIM 1的沉默则具有相反的作用。STIM 1在结直肠癌组织中的表达明显高于癌旁组织。STIM 1过表达与肿瘤分化程度低、淋巴结转移分期高有关。STIM 1阳性表达的结直肠癌患者预后差于STIM 1阴性表达的结直肠癌患者。此外，在CRC组织和细胞系中，STIM 1被发现是miR-185的直接靶点，miR-185是一种先前未报道参与EMT的微小RNA（miRNA）。总之，这些发现首次证明了STIM 1促进转移，并与CRC患者的癌症进展和预后不良相关。此外，我们表明，STIM 1的表达是由一个新的EMT相关的miRNA介导的转录后调控机制。这种新的miR-185-STIM 1轴促进CRC转移，可能是预后的候选生物标志物和新疗法的靶点。
STIM1 (stromal interaction molecule 1), an endoplasmic reticulum Ca 2+ sensor that triggers the store-operated Ca 2+ entry activation, has recently been implicated in cancer progression. However, the role of STIM1 in the progression and metastasis of colorectal cancer (CRC) has not been addressed. In this study, we confirmed increased expression of STIM1 in highly invasive CRC cell lines. Enhanced expression of STIM1 promoted CRC cell metastasis in vitro and in vivo, whereas silencing of STIM1 with small interfering RNA resulted in reduced metastasis. Ectopic expression of STIM1 in CRC cells induced epithelial-to-mesenchymal transition (EMT), whereas silencing of STIM1 had the opposite effect. Furthermore, STIM1 expression was markedly higher in CRC tissues than in adjacent noncancerous tissues. STIM1 overexpression correlated with poor differentiation and higher tumor node metastasis stage. CRC patients with positive STIM1 expression had poorer prognoses than those with negative STIM1 expression. Moreover, STIM1 was found to be a direct target of miR-185, a microRNA (miRNA) that has not previously been reported to be involved in EMT, in both CRC tissues and cell lines. Taken together, these findings demonstrate for the first time that STIM1 promotes metastasis and is associated with cancer progression and poor prognosis in patients with CRC. In addition, we show that expression of STIM1 is regulated by a posttranscriptional regulatory mechanism mediated by a new EMT-related miRNA. This novel miR-185–STIM1 axis promotes CRC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.