Long non-coding RNA tumor protein 73 antisense RNA 1 influences an interaction between lysine demethylase 5A and promoter of tumor protein 73 to enhance the malignancy of colorectal cancer.

IF 4.3 3区生物学

Human Cell Pub Date : 2022-09-01 Epub Date: 2022-07-27 DOI:10.1007/s13577-022-00740-2

Zhe Huang, He Wang, Mingli Yang

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引用次数: 1

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The aim of the present study was to explore the expression level of tumor protein 73 (TP73) in highly malignant CRC tumors and how the long non-coding RNA tumor protein 73 antisense RNA 1 (TP73-AS1) influences that transcription. We found that TP73-AS1 was highly expressed in malignant CRC samples in The Cancer Genome Atlas (TCGA) database. We also demonstrated TP73-AS1 was expressed in thirty samples of CRC tissues collected from China Medical University patients as well as in HCT116, RKO and SW480 CRC cell lines but not in HCoEpiC or CCD-18Co normal colon cells. Only wild-type TP73-AS1, but not any of its alternate splicing isoforms, was positively correlated with tumor malignancy. TP73-AS1 transcripts were shown to be located in cell nuclei especially in close proximity to the TP73 promoter in CRC cells, but not in normal colon cells. In addition, an interaction between lysine demethylase 5A (KDM5A) and TP73-AS1 in CRC cells, but not normal colon cells, and KDM5A localization on the TP73 promoter were influenced by TP73-AS1. Interestingly, the H3K4me3 level on the TP73 promoter was reduced, but was elevated by TP73-AS1 knockdown in CRC cells. In conclusion, these results suggest a novel epigenetic role of TP73-AS1 on histone demethylation that influences TP73 transcription, and shed light on malignancy in CRC.

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长链非编码RNA肿瘤蛋白73反义RNA 1影响赖氨酸去甲基酶5A与肿瘤蛋白73启动子的相互作用，增强结直肠癌的恶性程度。

结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。本研究旨在探讨肿瘤蛋白73 (tumor protein 73, TP73)在高度恶性CRC肿瘤中的表达水平，以及长链非编码RNA肿瘤蛋白73反义RNA 1 (tumor protein 73- as1)对其转录的影响。我们在癌症基因组图谱(TCGA)数据库中发现TP73-AS1在恶性结直肠癌样本中高表达。我们还证实TP73-AS1在从中国医科大学患者收集的30份结直肠癌组织样本以及HCT116、RKO和SW480结直肠癌细胞系中表达，但在HCoEpiC或CCD-18Co正常结肠细胞中不表达。只有野生型TP73-AS1与肿瘤恶性程度呈正相关，而其任何替代剪接异构体均与肿瘤恶性程度呈正相关。在结直肠癌细胞中，TP73- as1转录本位于细胞核中，尤其是靠近TP73启动子的位置，而在正常结肠细胞中则不存在。此外，结直肠癌细胞中赖氨酸去甲基化酶5A (KDM5A)与TP73- as1的相互作用，而正常结肠细胞中不存在这种相互作用，TP73- as1也影响了KDM5A在TP73启动子上的定位。有趣的是，在结直肠癌细胞中，TP73启动子上的H3K4me3水平降低，但由于TP73- as1的敲低而升高。总之，这些结果提示TP73- as1在组蛋白去甲基化中具有新的表观遗传作用，从而影响TP73的转录，并为结直肠癌的恶性肿瘤提供了线索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.