Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer.
Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer.
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PIWI 相互作用 RNA (piRNA) 作为疾病进展的致癌介质以及结直肠癌潜在预后生物标志物的新证据
DOI：
10.1186/s12943-018-0767-3
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发表时间：
2018-01-30
期刊：
影响因子：
37.3
通讯作者：
Goel A
中科院分区：
文献类型：
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作者：
Weng W;Liu N;Toiyama Y;Kusunoki M;Nagasaka T;Fujiwara T;Wei Q;Qin H;Lin H;Ma Y;Goel A
BackgroundEmerging evidence suggests that PIWI interacting RNAs（piRNAs）may be important epigenetic regulators of gene expression in human cancers; however，their functional and clinical significance in colorectal cancer（CRC）remains unknown.MethodsWe performed皮尔纳expression profiling in pairing cancer and normal tissues through small RNA-sequencing.研究了候选piRNA的临床意义，并在来自三个独立群组的771名CRC患者中独立验证。piRNA的生物学功能的特点是在细胞系中，其次是下游靶基因在CRC tissues.ResultsWe鉴定和验证piR-1245作为一种新的和经常过度表达的非编码RNA在CRC中，其表达与晚期和转移性疾病显着相关。piR-1245高表达患者的总生存期显著缩短，多变量分析表明其表达可作为CRC的独立预后生物标志物。在功能上，piR-1245作为癌基因并促进肿瘤进展，并且基因表达谱分析结果鉴定了一组参与调节细胞存活途径的下游靶基因。基于皮尔纳：mRNA序列的互补性，我们确定了一个面板的肿瘤抑制基因（ATF 3，BTG 1，DUSP 1，FAS，NFKBIA，UPP 1，SESN 2，TP 53 INP 1和MDX 1）作为piR-1245的直接目标，并成功地验证了它们的表达和piR-1245在CRC.ConclusionsWe之间的负相关性首次确定了一个PIWI相互作用的非编码RNA，piR-1245，作为一种新的癌基因和潜在的预后生物标志物在结直肠癌的作用。
BackgroundEmerging evidence suggests that PIWI-interacting RNAs (piRNAs) may be important epigenetic regulators of gene expression in human cancers; however, their functional and clinical significance in colorectal cancer (CRC) remains unknown.MethodsWe performed piRNA expression profiling in paired cancer and normal tissues through small RNA-sequencing. The clinical significance of candidate piRNAs was investigated, and independently validated in 771 CRC patients from three independent cohorts. The biological function of piRNAs was characterized in cell lines, followed by identification and validation of downstream target genes in CRC tissues.ResultsWe identified piR-1245 as a novel and frequently overexpressed noncoding RNA in CRC, and its expression significantly correlated with advanced and metastatic disease. Patients with high piR-1245 expression experienced significantly shorter overall survival, and multivariate analysis identified its expression to serve as an independent prognostic biomarker in CRC. Functionally, piR-1245 acts as an oncogene and promotes tumor progression, and gene expression profiling results identified a panel of downstream target-genes involved in regulating cell survival pathway. Based upon piRNA:mRNA sequence complementarity, we identified a panel of tumor suppressor genes (ATF3, BTG1, DUSP1, FAS,NFKBIA, UPP1, SESN2, TP53INP1 and MDX1) as direct targets of piR-1245, and successfully validated an inverse correlation between their expression and piR-1245 in CRC.ConclusionsWe for the first time have identified the role for a PIWI-interacting noncoding RNA, piR-1245, as a novel oncogene and a potential prognostic biomarker in colorectal cancer.
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影响因子：
--
作者：
Navarro A;Tejero R;Viñolas N;Cordeiro A;Marrades RM;Fuster D;Caritg O;Moises J;Muñoz C;Molins L;Ramirez J;Monzo M
通讯作者：
Monzo M
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
24.5
作者：
Han TS;Hur K;Xu G;Choi B;Okugawa Y;Toiyama Y;Oshima H;Oshima M;Lee HJ;Kim VN;Chang AN;Goel A;Yang HK
通讯作者：
Yang HK
影响因子：
9.7
作者：
Glinsky, GV;Glinsky, VV;Hueser, CJ
通讯作者：
Hueser, CJ
影响因子：
4
作者：
Siddiqi, Sara;Matushansky, Igor
通讯作者：
Matushansky, Igor