Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer.
Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer.
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DOI：
10.1038/s41598-018-25320-z
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发表时间：
2018-05-08
影响因子：
4.6
通讯作者：
Lupold SE
中科院分区：
文献类型：
--
作者：
Kumar B;Rosenberg AZ;Choi SM;Fox-Talbot K;De Marzo AM;Nonn L;Brennen WN;Marchionni L;Halushka MK;Lupold SE
miR-1和miR-143在人前列腺癌（PCa）中经常减少，而miR-141和miR-21经常升高。因此，这些miRNA已被研究为细胞自主肿瘤抑制因子和癌基因。然而，这些miRNAs的细胞类型特异性在前列腺组织中并没有很好的定义。通过两种不同的显微切割技术和液滴数字RT-PCR，我们定量了根治性乳腺癌切除术标本的基质和上皮中的这些miRNA。与其作为细胞自主肿瘤抑制因子的作用相反，我们发现miR-1和miR-143的表达主要是基质。相反，miR-141主要是上皮细胞。miR-21在间质和上皮中均被检测到。引人注目的是，miR-1和miR-143的水平在肿瘤相关基质中显著降低，但在肿瘤上皮中没有。人细胞系、组织和前列腺源性基质培养物中的基因表达分析支持miR-1、miR-141和miR-143的细胞类型选择性表达。PCa基因组图谱（TCGA-PRAD）分析显示，基质标记物与miR-1和miR-143之间存在强正相关性，基质标记物与miR-141之间存在强负相关性。在这些肿瘤中，miR-1的丢失和miR-21的获得与生化复发高度相关。这些数据为PCa肿瘤微环境中基质和上皮miRNA表达提供了新的线索。
MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
28.2
作者：
Dimitrova N;Gocheva V;Bhutkar A;Resnick R;Jong RM;Miller KM;Bendor J;Jacks T
通讯作者：
Jacks T
DOI：
10.1002/pros.23145
发表时间：
2016-05
期刊：
The Prostate
影响因子：
--
作者：
Brennen WN;Kisteman LN;Isaacs JT
通讯作者：
Isaacs JT
影响因子：
8.8
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
通讯作者：
Seki, N.
影响因子：
14.9
作者：
Kent OA;McCall MN;Cornish TC;Halushka MK
通讯作者：
Halushka MK