Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma.
Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma.
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DOI：
10.3892/ijo.2013.1851
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发表时间：
2013-05
影响因子：
5.2
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Yamamoto N;Kinoshita T;Nohata N;Itesako T;Yoshino H;Enokida H;Nakagawa M;Shozu M;Seki N
宫颈癌是女性最常见的癌症之一。每年有超过275，100名妇女死于宫颈癌。宫颈鳞状细胞癌（cervical squamous cell carcinoma，SCC）是宫颈癌中最常见的类型之一，与高危型人乳头状瘤病毒（human papilloma virus，HPV）相关，尽管HPV感染本身可能不足以诱发恶性转化。MicroRNA（miRNAs）是一类小的非编码RNA，通过抑制翻译或切割RNA转录物来调控蛋白质编码基因的表达。越来越多的证据表明，miRNAs参与了宫颈鳞癌的进展、发展和转移。SCC（下咽SCC和食管SCC）中的miRNA表达特征显示，与邻近的非癌上皮相比，miR-218在癌组织中的表达显著降低，表明miR-218是候选的肿瘤抑制因子。本研究的目的是研究miR-218在宫颈鳞癌中的功能意义，并确定宫颈鳞癌中miR-218介导的新癌症途径。在HPV阳性和HPV阴性宫颈SCC细胞系中，miR-218的恢复显著抑制癌细胞的迁移和侵袭。这些数据表明miR-218在宫颈SCC中起肿瘤抑制剂的作用。我们的计算机模拟分析表明，miR-218似乎是肿瘤细胞过程的重要调节剂，通过抑制许多靶点，特别是参与黏着斑信号通路的靶点。基因表达数据表明，LAMB 3，一种已知影响细胞分化，迁移，粘附，增殖和存活的层粘连蛋白，在宫颈SCC临床标本中上调，沉默研究表明，LAMB 3在宫颈SCC中作为癌基因发挥作用。新的肿瘤抑制性miR-218介导的分子通路的鉴定为宫颈SCC的肿瘤发生和转移提供了新的见解。
Cervical cancer is one of the most common cancers in women. More than 275,100 women die from cervical cancer each year. Cervical squamous cell carcinoma (cervical SCC), one of the most frequent types of cervical cancers, is associated with high-risk human papilloma virus (HPV), although HPV infection alone may not be enough to induce malignant transformation. MicroRNAs (miRNAs), a class of small non-coding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to cervical SCC progression, development and metastasis. miRNA expression signatures in SCC (hypopharyngeal SCC and esophageal SCC) revealed that miR-218 expression was significantly reduced in cancer tissues compared with adjacent non-cancerous epithelium, suggesting that miR-218 is a candidate tumor suppressor. The aim of this study was to investigate the functional significance of miR-218 in cervical SCC and to identify novel miR-218-mediated cancer pathways in cervical SCC. Restoration of miR-218 significantly inhibited cancer cell migration and invasion in both HPV-positive and HPV-negative cervical SCC cell lines. These data indicated that miR-218 acts as a tumor suppressor in cervical SCC. Our in silico analysis showed that miR-218 appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in focal adhesion signaling pathways. Gene expression data indicated that LAMB3, a laminin protein known to influence cell differentiation, migration, adhesion, proliferation and survival, was upregulated in cervical SCC clinical specimens, and silencing studies demonstrated that LAMB3 functioned as an oncogene in cervical SCC. The identification of novel tumor-suppressive miR-218-mediated molecular pathways has provided new insights into cervical SCC oncogenesis and metastasis.
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影响因子：
11.4
作者：
BAND, V;DALAL, S;ANDROPHY, EJ
通讯作者：
ANDROPHY, EJ
影响因子：
3.7
作者：
Pereira PM;Marques JP;Soares AR;Carreto L;Santos MA
通讯作者：
Santos MA
影响因子：
11.5
作者：
Lee, Jeong-Won;Choi, Chel Hun;Bae, Duk-Soo
通讯作者：
Bae, Duk-Soo
影响因子：
--
作者：
Kinoshita T;Hanazawa T;Nohata N;Kikkawa N;Enokida H;Yoshino H;Yamasaki T;Hidaka H;Nakagawa M;Okamoto Y;Seki N
通讯作者：
Seki N
DOI：
10.1016/j.urolonc.2010.05.008
发表时间：
2012-07-01
影响因子：
2.7
作者：
Chiyomaru, Takeshi;Enokida, Hideki;Nakagawa, Masayuki
通讯作者：
Nakagawa, Masayuki