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长链非编码 RNA AC087388.1 作为结直肠癌的新型生物标志物。

Long non-coding RNA AC087388.1 as a novel biomarker in colorectal cancer.

机构信息

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

BMC Cancer. 2022 Feb 21;22(1):196. doi: 10.1186/s12885-022-09282-0.

Abstract

BACKGROUND

Several investigations have reported diverse roles of long non-coding RNA (lncRNA) in biological processes, tumor development, and progression of colorectal cancer (CRC). In this study, we investigated the lncRNA AC087388.1 tumorigenic role in CRC cells.

METHODS

The CRC tissues were collected at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. The human SW-48 and HT-29 CRC cell lines were obtained from the national cell bank of Iran. The cells were cultured according to ATCC (the American Type Culture Collection) recommendations. Quantitative real-time PCR was applied to assess the RNA expression. ShRNA transfection was done to downregulate the target gene. MTT and apoptosis assays were conducted to evaluate cell proliferation and viability, respectively. Colony formation assay, wound healing assay, and invasion assay were applied to determine growth, motility, and invasion of the cells, respectively. ENCORI online tool was used as downstream enrichment analysis.

RESULTS

Forty CRC patients were encompassed in this study. The results demonstrated that the lncRNA SLC16A1-AS1, AC087388.1, and ELFN1-AS1 were significantly overexpressed in the CRC tissues in comparison to their normal counterpart margins. All the lncRNAs have shown significant Area Under Curve (AUC) values in the patients. Downregulation of lncRNA AC087388.1 remarkably decreased the cell proliferation and viability of the CRC cells. In addition, the data demonstrated that the downregulation of lncRNA AC087388.1 significantly suppressed cell growth and colony formation capability in the cells. Also, downregulation of lncRNA AC087388.1 attenuated motility and invasion of CRC cells, and significantly decreased the expression of invasion genes. In-silico functional enrichment analysis indicated that the lncRNA AC087388.1 has contributed to crucial signaling pathways in tumorigenesis such as the p53 and Wnt signaling pathways, apoptosis, and cell cycle.

CONCLUSIONS

Altogether, we showed that lncRNA AC087388.1 has an oncogenic role in tumorigenesis of CRC, and it can be considered as a novel diagnostic and prognostic biomarker in CRC.

摘要

背景

多项研究报告称,长非编码 RNA(lncRNA)在生物过程、肿瘤发生和结直肠癌(CRC)进展中具有多种作用。在这项研究中,我们研究了 lncRNA AC087388.1 在 CRC 细胞中的致瘤作用。

方法

CRC 组织取自伊朗马什哈德的 Reza 放射肿瘤学和肿瘤中心。人 SW-48 和 HT-29 CRC 细胞系购自伊朗国家细胞库。根据 ATCC(美国模式培养物集存库)建议培养细胞。应用定量实时 PCR 评估 RNA 表达。转染 shRNA 下调靶基因。MTT 和凋亡实验分别用于评估细胞增殖和活力。集落形成实验、划痕愈合实验和侵袭实验分别用于测定细胞的生长、迁移和侵袭。使用 ENCORI 在线工具作为下游富集分析。

结果

本研究纳入了 40 名 CRC 患者。结果表明,与正常对照边缘相比,CRC 组织中 lncRNA SLC16A1-AS1、AC087388.1 和 ELFN1-AS1 显著过表达。所有 lncRNA 在患者中均表现出显著的曲线下面积(AUC)值。下调 lncRNA AC087388.1 显著降低了 CRC 细胞的增殖和活力。此外,数据表明,下调 lncRNA AC087388.1 显著抑制了细胞的生长和集落形成能力。此外,下调 lncRNA AC087388.1 减弱了 CRC 细胞的迁移和侵袭能力,并显著降低了侵袭基因的表达。体内功能富集分析表明,lncRNA AC087388.1 有助于肿瘤发生中的关键信号通路,如 p53 和 Wnt 信号通路、细胞凋亡和细胞周期。

结论

综上所述,我们表明 lncRNA AC087388.1 在 CRC 的肿瘤发生中具有致癌作用,它可以作为 CRC 的一种新的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e9/8862536/5bafd3a9066b/12885_2022_9282_Fig1_HTML.jpg

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