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三葉草王鐵蟲 (正式寫手)
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[求助]
英譯漢,謝謝
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Desjobert et al. showed that the expression of miR-29a was regulated by methylation and suggested the existence of a positive feedback loop involving DNMT3b [17]. Our data extend these observations and show that miR-29b expression is upregulated in response to treatment with a demethylating agent, which supports the presence of a positive feedback loop in NSCLC cells. However, a similar regulation of expression by methylation was not observed for miR-29c. This could be attributed to the fact that miR-29c and miR-29b2 is expressed from a different locus (Chr 1q32.2) and the regulation pattern may be different from that of miR-29a and miR-29b1 on chromosome 7. In addition, a different positive feedback loop regulating the expression of miR-29s via c-Myc has been proposed. The effect of the c-Myc oncogene on the repression of mir-29 promoter activity has been shown previously [16,31]. Furthermore, this occurs downstream of the Wnt pathway and could be activated byb-catenin. Therefore, miR-29s may indirectly suppress the transcription of c-Myc by modulating the Wnt/ b-catenin signaling pathway. In summary, we showed that DNMT3A and DNMT3B are involved in the down-regulation of WIF-1 expression and that miR-29s restore WIF-1 expression by suppressing DNMT3A and DNMT3B. Enforced expression of these miRNAs in lung cancer cells blocks Wnt/b-catenin signaling and inhibits tumor growth. In addition, the expression of miR-29a and miR-29b may be partly regulated by DNMT3A and DNMT3B in a positive feedback loop. Our study provides new insights into the involvement of miRNAs in the Wnt pathway and underscores the fundamental role of these miRNAs as tumor suppressor genes. |

至尊木蟲 (知名作家)
Translator and Proofreader
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Desjobert等(研究)表明,miR-29a的表達受甲基化調(diào)節(jié),并指出(提示)有一由DNMT3b參與的正反饋環(huán)路存在[17]。我們的結果進一步拓展了這些(已經(jīng)報告了的)觀察結果,而且顯示用去甲基化試劑處理可以引起miR-29b的向上調(diào)節(jié),這(一發(fā)現(xiàn))支持在NSCLC細胞中存在一正反饋環(huán)路。然而,并未觀察到甲基化對miR-29c的表達有類似調(diào)節(jié)作用。這可能是由于miR-29c和miR-29b2是在不同位點上(1號染色體q32.2)表達的,其(表達)調(diào)節(jié)形式可能與位于7號染色體上的miR-29a和miR-29b1不同。此外,(有人)提出了調(diào)節(jié)miR-29s表達的另外一種由c-Myc參與的正反饋環(huán)路。以前的結果已經(jīng)表明,c-Myc癌基因?qū)iR-29啟動子活性有抑制作用 [16,31]。而且,該作用發(fā)生于Wnt信號通路下游,并且可以被β-cateni激活。因此,miR-29s可能通過調(diào)節(jié)Wnt/β-catenin信號通路而間接抑制c-Myc的轉(zhuǎn)錄。 總之,我們(的結果)表明,DNMT3A和DNMT3B參與WIF-1表達的向下調(diào)節(jié),而且miR-29s可以通過抑制DNMT3A和DNMT3B而恢復WIF-1的表達。讓肺癌細胞強行表達這些miRNA(即miR-29s)可以阻斷Wnt/β-catenin信號通路并抑制腫瘤生長。另外,在這一正反饋環(huán)路中,miR-29a和miR-29b的表達可能受DNMT3A和DNMT3B的部分調(diào)節(jié)。我們的研究對miRNA參與Wnt信號通路提供了新的見解,并強調(diào)了這些miRNA作為腫瘤抑制基因的基本作用。 |
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