Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer.
Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer.
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DOI：
10.1186/1476-4598-12-163
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发表时间：
2013-12-13
期刊：
影响因子：
37.3
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Li L;Luo J;Wang B;Wang D;Xie X;Yuan L;Guo J;Xi S;Gao J;Lin X;Kong Y;Xu X;Tang H;Xie X;Liu M
MicroRNAs（miRNAs）在肿瘤发生发展中起重要作用。在这项研究中，我们研究了miR-124在乳腺癌中的作用，并阐明了miR-124对flotillin-1（FLOT 1）的调控。使用定量逆转录-PCR检测乳腺癌细胞系和患者标本中miR-124的表达水平。随后分析所得数据的临床病理学意义。接下来，我们探索了miR-124的功能，以确定其在体外癌细胞生长和迁移中的潜在作用。进行荧光素酶报告基因测定以确认miR-124的靶基因，并在细胞系和患者标本中验证结果。我们发现miR-124在乳腺癌细胞系和患者标本中的表达分别与正常细胞系和配对的相邻正常组织相比显著下调（P < 0.0001）。miR-124与肿瘤的TNM分期（P = 0.0007）和淋巴结转移（P = 0.0004）相关。在乳腺癌细胞系中，miR-124的异位表达在体外抑制细胞生长和迁移。此外，我们确定FLOT 1基因是miR-124的一个新的直接靶点，miR-124的异位表达显著抑制FLOT 1。荧光素酶检测证实miR-124可直接与FLOT 1的3′非翻译区结合，抑制FLOT 1的翻译。此外，FLOT 1在乳腺癌组织中广泛上调，并与miR-124呈负相关。与miR-124的作用一致，FLOT 1的敲低显著抑制乳腺癌细胞的生长和迁移。我们还观察到，FLOT 1的救援表达部分恢复了miR-124的作用。我们的研究表明miR-124可能通过调控FLOT 1在乳腺癌中发挥抑癌作用。这种microRNA可以作为乳腺癌的潜在诊断标志物和治疗靶点。
MicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124. The expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens. We found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124. Our study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.
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DOI：
10.1186/bcr2839
发表时间：
2011-03-04
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hannafon BN;Sebastiani P;de las Morenas A;Lu J;Rosenberg CL
通讯作者：
Rosenberg CL
影响因子：
11.5
作者：
Gong, Hui;Song, Libing;Li, Jun
通讯作者：
Li, Jun
MiR-34a通过下调Bcl-2和SIRT1抑制乳腺癌的增殖和迁移
影响因子：
4.6
作者：
Li, Laisheng;Yuan, Linjin;Xie, Xiaoming
通讯作者：
Xie, Xiaoming
影响因子：
11.5
作者：
Chan, Maurice;Liaw, Chiew Suan;Lee, Ann Siew-Gek
通讯作者：
Lee, Ann Siew-Gek
FLOT1 的敲低通过 FOXO3a 的上调损害乳腺癌中的细胞增殖和致瘤性
影响因子：
11.5
作者：
Lin, Chuyong;Wu, Zhiqiang;Song, Libing
通讯作者：
Song, Libing