Pyknon-Containing Transcripts Are Downregulated in Colorectal Cancer Tumors, and Loss of PYK44 Is Associated With Worse Patient Outcome.

Pyknon-Containing Transcripts Are Downregulated in Colorectal Cancer Tumors, and Loss of PYK44 Is Associated With Worse Patient Outcome.
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DOI:
10.3389/fgene.2020.581454
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发表时间:
2020
影响因子:
3.7
通讯作者:
Reis RM
Reis RM
中科院分区:
生物学3区
文献类型:
--
作者:
Evangelista AF;de Menezes WP;Berardinelli GN;Dos Santos W;Scapulatempo-Neto C;Guimarães DP;Calin GA;Reis RM

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Pyknon是人类/灵长类动物特异性DNA基序,至少16个核苷酸长,在基因组的基因间和内含子区域中重复,并且可以位于一类新的可变长度的非编码RNA中。最近的研究报道,pyknon失调可能参与了包括结直肠癌在内的致癌过程。我们评估了一组分子特征的结直肠癌(CRC)患者的一组12个蛋白激酶的表达谱。通过qRT-PCR测定了绿脓杆菌(PYK 10、PYK 14、PYK 17、PYK 26、PYK 27、PYK 40、PYK 41、PYK 42、PYK 43、PYK 44、PYK 83和PYK 90)的表达。对20例病例进行了初步分析,获得了PYK 10、PYK 17、PYK 42、PYK 44和PYK 83的一致结果。此外,在73例CRC病例中评估了所选绿脓杆菌的表达。此外,在52例患者中,我们比较了肿瘤和正常组织中的表达谱。与正常组织相比,分析的所有五种蟒蛇在肿瘤中的表达水平显着降低。观察到PYK 10的表达与TP 53突变(p = 0.029)、PYK 17的表达与组织学分级(p = 0.035)以及PYK 44的表达与临床分期(p = 0.016)之间存在关联。此外,PYK 44的水平与患者较差的总体存活率显著相关(p = 0.04)。我们报道了与正常组织相比,肿瘤组织中的蛋白激酶基序的显著下调,以及较低的PYK 44表达与患者预后较差的相关性。需要进一步的研究来扩展和验证这些发现,并确定临床病理学影响。
Pyknons are specific human/primate-specific DNA motifs at least 16 nucleotides long that are repeated in blocks in intergenic and intronic regions of the genome and can be located in a new class of non-coding RNAs of variable length. Recent studies reported that pyknon deregulation could be involved in the carcinogenesis process, including colorectal cancer. We evaluated the expression profile of a set of 12 pyknons in a set of molecularly characterized colorectal cancer (CRC) patients. The pyknons (PYK10, PYK14, PYK17, PYK26, PYK27, PYK40, PYK41, PYK42, PYK43, PYK44, PYK83, and PYK90) expression was determined by qRT-PCR. A pilot analysis of 20 cases was performed, and consistent results were obtained for PYK10, PYK17, PYK42, PYK44, and PYK83. Further, the expression of the selected pyknons was evaluated in 73 CRC cases. Moreover, in 52 patients, we compared the expression profile in both tumor and normal tissues. All five pyknons analyzed showed significantly lower expression levels in the tumor compared to normal tissue. It was observed an association between expression of PYK10 with TP53 mutations (p = 0.029), PYK17 to histologic grade (p = 0.035), and PYK44 to clinical staging (p = 0.016). Moreover, levels of PYK44 were significantly associated with the patient's poor overall survival (p = 0.04). We reported the significant downregulation of pyknons motifs in tumor tissue compared with the normal counterpart, and the association of lower PYK44 expression with worse patient outcome. Further studies are needed to extend and validate these findings and determine the clinical-pathological impact.
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