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新型长非编码 RNA 的上调可能对 CYP24A1 和 PFDN4 生物标志物在人结直肠癌中的作用具有协同效应。

Novel long noncoding RNAs upregulation may have synergistic effects on the CYP24A1 and PFDN4 biomarker role in human colorectal cancer.

机构信息

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

Department of Gastrointestinal Cancer, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Physiol. 2021 Mar;236(3):2051-2057. doi: 10.1002/jcp.29992. Epub 2020 Aug 2.

DOI:10.1002/jcp.29992
PMID:32743796
Abstract

Long noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism pathway. In the present research, we surveyed the expression levels and clinical significance of novel lncRNAs related to CYP24A1 and PFDN4 genes in colorectal cancer (CRC) using real-time polymerase chain reaction. Furthermore, we assessed the expression of these genes after vitamin D treatment in HCT-116 and HT-29 colon cancer cell lines. Our results indicated that the transcription of CYP24A1, PFDN4, and nearby lncRNAs was affected by vitamin D treatment in HCT-116 and HT-29 cell lines. Moreover, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 were upregulated and had the potential to distinguish colorectal cancer tissues from the adjacent tissues by the large area under the receiver operating characteristic curve (0.94, 0.66, 0.70, and 0.60, respectively). lnc-TSHZ2-19:1 expression level significantly correlated with gender (p = .03). In conclusion, CYP24A1, PFDN4, lnc-CYP24A1-3:1, and lnc-TSHZ2-19:1 can be used as potential diagnostic biomarkers in the specific and sensitive assessment of CRC. Besides this, vitamin D treatment may modulate the expression of these genes in a cell-specific manner.

摘要

长链非编码 RNA(lncRNA)正在成为肿瘤起始、增殖和转移的主要调控因子;然而,它们作为潜在生物标志物的诊断价值仍需阐明。维生素 D 影响多种途径中几个基因的表达,包括维生素 D 代谢途径中的 CYP24A1 基因。在本研究中,我们使用实时聚合酶链反应调查了与 CYP24A1 和 PFDN4 基因相关的新型 lncRNA 在结直肠癌(CRC)中的表达水平及其临床意义。此外,我们评估了维生素 D 处理后这些基因在 HCT-116 和 HT-29 结肠癌细胞系中的表达情况。我们的结果表明,CYP24A1、PFDN4 和附近 lncRNA 的转录受 HCT-116 和 HT-29 细胞系中维生素 D 处理的影响。此外,CYP24A1、PFDN4、lnc-CYP24A1-3:1 和 lnc-TSHZ2-19:1 上调,通过大的受试者工作特征曲线下面积(分别为 0.94、0.66、0.70 和 0.60)具有区分结直肠癌组织与相邻组织的潜力。lnc-TSHZ2-19:1 表达水平与性别显著相关(p=0.03)。总之,CYP24A1、PFDN4、lnc-CYP24A1-3:1 和 lnc-TSHZ2-19:1 可用作 CRC 特异性和敏感性评估的潜在诊断生物标志物。此外,维生素 D 处理可能以细胞特异性方式调节这些基因的表达。

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