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PCAT1:多种癌症中的致癌 lncRNA 及其潜在的治疗靶点。

PCAT1: An oncogenic lncRNA in diverse cancers and a putative therapeutic target.

机构信息

Urology and Nephrology Research Center(Ghafouri-Fard et al., 2020b), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Exp Mol Pathol. 2020 Jun;114:104429. doi: 10.1016/j.yexmp.2020.104429. Epub 2020 Mar 24.

Abstract

The critical roles of long non-coding RNAs (lncRNAs) in the regulation of diverse biological functions has potentiated them as cancer biomarkers. Among these transcripts is the prostate cancer associated transcript 1 (PCAT1) which has been initially shown to exert oncogenic roles in prostate cancer. Further studies revealed its similar roles in various kinds of human malignancies including both solid tumors and hematological malignancies. Animal studies have shown that down-regulation of this lncRNA can attenuate tumor growth in a wide array of cancers including prostate cancer, colorectal cancer, squamous cell carcinoma lung cancer and hepatocellular carcinoma. Studies aimed at identification of diagnostic value of this lncRNA in human cancers reported various values ranging from 0.66 to 0.89 in diverse cancers with the best value reported in multiple myeloma. This lncRNA has a number of putative functional genomic variants such as rs1902432, rs2632159, rs1026411, rs710886, rs16901904 and rs710886 which can modify expression or function of PCAT1 thus altering the risk of human cancers. Based on aberrant expression of PCAT1 in malignancies of diverse origins, this lncRNA can be regarded as a therapeutic target in a vast array of cancers. Thus, modalities for efficient reduction of its expression would be beneficial for several patients.

摘要

长链非编码 RNA(lncRNAs)在调节多种生物功能中的关键作用使它们成为癌症的生物标志物。在这些转录本中,前列腺癌相关转录物 1(PCAT1)最初被证明在前列腺癌中具有致癌作用。进一步的研究揭示了它在各种人类恶性肿瘤中的类似作用,包括实体瘤和血液恶性肿瘤。动物研究表明,下调这种 lncRNA 可以在包括前列腺癌、结直肠癌、鳞状细胞肺癌和肝细胞癌在内的广泛癌症中减弱肿瘤生长。旨在确定这种 lncRNA 在人类癌症中的诊断价值的研究报告了在不同癌症中从 0.66 到 0.89 不等的各种价值,在多发性骨髓瘤中报告的最佳价值最高。这种 lncRNA 有许多假定的功能性基因组变异,如 rs1902432、rs2632159、rs1026411、rs710886、rs16901904 和 rs710886,它们可以修饰 PCAT1 的表达或功能,从而改变人类癌症的风险。基于 PCAT1 在不同来源恶性肿瘤中的异常表达,这种 lncRNA 可以被视为广泛癌症的治疗靶点。因此,有效降低其表达的方法将有益于许多患者。

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