RNA editing in RHOQ promotes invasion potential in colorectal cancer
RNA editing in RHOQ promotes invasion potential in colorectal cancer
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DOI：
10.1084/jem.20132209
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发表时间：
2014-04-07
影响因子：
15.3
通讯作者：
Kim, Tae-You
中科院分区：
文献类型：
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作者：
Han, Sae-Won;Kim, Hwang-Phill;Kim, Tae-You
RNA编辑可以在不改变DNA序列的情况下增加RNA序列的变异性。通过比较直肠癌的全基因组和转录组序列数据，我们发现ras同源家族成员Q(RHOQ)转录本中与肿瘤相关的RNA编辑增加。腺苷到肌苷(A到I)的编辑导致在残基136处用丝氨酸取代天冬氨酸。我们观察到结直肠癌(CRC)组织中RHOQ RNA的编辑水平高于正常组织。在结直肠癌细胞系中，RNA编辑程度与RhoQ蛋白活性有关。RhoQ N136S氨基酸替换增加了RhoQ活性、肌动蛋白细胞骨架重组和侵袭潜能。KRAS突变进一步增加了RhoQ N136S的体外侵袭能力。在结直肠癌患者中，具有编辑RHOQ转录本和KRAS基因突变的肿瘤患者更容易复发。综上所述，我们表明RNA编辑是促成CRC进展的另一种序列改变机制。
RNA editing can increase RNA sequence variation without altering the DNA sequence. By comparing whole-genome and transcriptome sequence data of a rectal cancer, we found novel tumor-associated increase of RNA editing in ras homologue family member Q (RHOQ) transcripts. The adenosine-to-inosine (A-to-I) editing results in substitution of asparagine with serine at residue 136. We observed a higher level of the RHOQ RNA editing in tumor compared with normal tissue in colorectal cancer (CRC). The degree of RNA editing was associated with RhoQ protein activity in CRC cancer cell lines. RhoQ N136S amino acid substitution increased RhoQ activity, actin cytoskeletal reorganization, and invasion potential. KRAS mutation further increased the invasion potential of RhoQ N136S in vitro. Among CRC patients, recurrence was more frequently observed in patients with tumors having edited RHOQ transcripts and mutations in the KRAS gene. In summary, we show that RNA editing is another mechanism of sequence alteration that contributes to CRC progression.