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新型 Notch 诱导的长非编码 RNA LUNAR1 决定结直肠癌的增殖和预后。

The Novel Notch-induced Long Noncoding RNA LUNAR1 Determines the Proliferation and Prognosis of Colorectal Cancer.

机构信息

Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Sci Rep. 2019 Dec 27;9(1):19915. doi: 10.1038/s41598-019-56536-2.

Abstract

In contrast to what is known about the complicated roles of Notch signalling in human malignancies, the direct target genes of Notch signalling are still unclear. Recently, long noncoding RNAs (lncRNAs) have been found to play various roles in the post-transcriptional regulation of gene expression. In the present study, we investigated the potential role of the Notch-induced lncRNA LUNAR1 in colorectal cancer (CRC). We recruited 196 cases of clinical CRC specimens and investigated LUNAR1 levels in these specimens. The associations of LUNAR1 with tumour aggressiveness and clinical outcomes were evaluated. Moreover, the impact of LUNAR1 on the malignant behaviour of tumour cells was tested in cell lines. Significantly increased expression of LUNAR1 in clinical CRC specimens was detected compared with that in matching normal tissues. LUNAR1 expression in CRC was found to be associated with the tumour aggressiveness, disease-free survival and overall survival of patients. The downregulation of LUNAR1 in SW620 cells inhibited cell proliferation, migration, invasion and tumour growth while inducing apoptosis. Moreover, the inhibition of LUNAR1 can significantly suppress IGF1 signalling in CRC. These results indicated that LUNAR1 was increased in CRC and might promote tumour progression. Thus, LUNAR1 may constitute a promising prognostic marker for the clinical management of CRC.

摘要

与 Notch 信号在人类恶性肿瘤中复杂作用的已知情况相反, Notch 信号的直接靶基因仍不清楚。最近,长链非编码 RNA(lncRNA)已被发现可在基因表达的转录后调控中发挥多种作用。在本研究中,我们研究了 Notch 诱导的 lncRNA LUNAR1 在结直肠癌(CRC)中的潜在作用。我们招募了 196 例临床 CRC 标本,并检测了这些标本中的 LUNAR1 水平。评估了 LUNAR1 与肿瘤侵袭性和临床结局的相关性。此外,还在细胞系中测试了 LUNAR1 对肿瘤细胞恶性行为的影响。与匹配的正常组织相比,在临床 CRC 标本中检测到 LUNAR1 的表达显著增加。CRC 中的 LUNAR1 表达与患者的肿瘤侵袭性、无病生存期和总生存期相关。在 SW620 细胞中下调 LUNAR1 可抑制细胞增殖、迁移、侵袭和肿瘤生长,同时诱导细胞凋亡。此外,抑制 LUNAR1 可显著抑制 CRC 中的 IGF1 信号。这些结果表明 LUNAR1 在 CRC 中增加,可能促进肿瘤进展。因此,LUNAR1 可能成为 CRC 临床管理中有前途的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3e2/6934546/6c6ac1c2e38d/41598_2019_56536_Fig1_HTML.jpg

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