Extracellular miR-224 as a prognostic marker for clear cell renal cell carcinoma.
Extracellular miR-224 as a prognostic marker for clear cell renal cell carcinoma.
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DOI：
10.18632/oncotarget.22436
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Matsuyama H
中科院分区：
文献类型：
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作者：
Fujii N;Hirata H;Ueno K;Mori J;Oka S;Shimizu K;Kawai Y;Inoue R;Yamamoto Y;Matsumoto H;Shimabukuro T;Udoh K;Hoshii Y;Dahiya R;Matsuyama H
外泌体-miRNAs（exosome-miR）最近被鉴定为癌症进展和远处转移的调节剂。我们之前发现，细胞内miR-224上调，并与透明细胞肾细胞癌（ccRCC）的癌症侵袭和转移显著相关。因此，我们研究了外泌体miR-224在ccRCC中的作用，并探索了肾细胞癌中细胞内和细胞外miR-224之间的相互作用。为了验证从血液样品或细胞培养基中分离外泌体的方法，我们使用透射电子显微镜（TEM）检查外泌体形态。我们研究了108例ccRCC患者中exo-miR-224表达与患者预后之间的关系。我们从转移性肾癌细胞系中分离了外泌体，并通过几种功能分析测试了它们对原发性肾癌细胞系的影响。我们发现，与低表达组相比，高表达水平exo-miR-224组的无进展生存期、癌症特异性生存期和总生存期显著缩短。在多变量分析中，高水平的exo-miR-224是与所研究的所有疾病相关的显著风险因素。在将来自转移性RCC细胞系的外来体添加到原代RCC细胞系中后，细胞增殖和侵袭增加，而凋亡细胞的百分比显著降低。在原发性肾癌细胞系中，细胞内miR-224水平显著上调。外泌体中的细胞外miR-224影响患者预后，并且是ccRCC患者的潜在预后生物标志物。
Exosome-miRNAs (exo-miR) have recently been identified as modulators of cancer progression and distant metastasis. We previously found that intracellular miR-224 is up-regulated and significantly related to cancer invasion and metastasis in clear cell renal cell carcinoma (ccRCC). We therefore investigated the role of exosome miR-224 in ccRCC and explored the interaction between intra- and extracellular miR-224 in renal cell carcinoma. To validate the method for isolating exosomes from blood samples or cell culture media, we examined exosome morphology using transmission electron microscope (TEM). We investigated the relationship between exo-miR-224 expression and patient prognosis in 108 ccRCC patients. We isolated exosomes from a metastatic renal cancer cell line and tested their effects on a primary renal cancer cell line with several functional analyses. We found that the high expression level exo-miR-224 group has significantly shorter progression-free survival, cancer-specific survival, and overall survival compared with the low expression group. In multivariate analysis, a high level of exo-miR-224 was a significant risk factor related to all prognoses investigated. After adding exosomes from a metastatic RCC cell line to a primary RCC cell line, cell proliferation and invasion were increased while the percentage of apoptotic cells was significantly decreased. Intracellular levels of miR-224 were significantly up-regulated in the primary renal cancer cell line. Extracellular miR-224 in exosomes impacts on patient prognosis and is a potential prognostic biomarker for ccRCC patients.
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影响因子：
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作者：
Cui R;Kim T;Fassan M;Meng W;Sun HL;Jeon YJ;Vicentini C;Tili E;Peng Y;Scarpa A;Liang G;Zhang YK;Chakravarti A;Croce CM
通讯作者：
Croce CM
影响因子：
37.3
作者：
Frediani JN;Fabbri M
通讯作者：
Fabbri M
影响因子：
--
作者：
Liu H;Brannon AR;Reddy AR;Alexe G;Seiler MW;Arreola A;Oza JH;Yao M;Juan D;Liou LS;Ganesan S;Levine AJ;Rathmell WK;Bhanot GV
通讯作者：
Bhanot GV
影响因子：
10.5
作者：
Linehan WM;Bratslavsky G;Pinto PA;Schmidt LS;Neckers L;Bottaro DP;Srinivasan R
通讯作者：
Srinivasan R
影响因子：
6
作者：
Lichner, Zsuzsanna;Mejia-Guerrero, Salvador;Yousef, George M.
通讯作者：
Yousef, George M.