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miR-1297 下调预示着预后不良,并通过靶向 CREB1 促进胃癌细胞生长。

Downregulation of MiR-1297 predicts poor prognosis and enhances gastric cancer cell growth by targeting CREB1.

机构信息

Traditional Chinese Medical University, Hangzhou, Zhejiang, 310005, China; The Second Clinical Medical College of Zhejiang Traditional, Chinese Medical University, Hangzhou, Zhejiang, 310005, China; Pang Dexiang Famous Chinese Medical Studio of Zhejiang Province, Hangzhou, Zhejiang, 310005, China; Oncology Department of Xinhua Hospital in Zhejiang Province, Hangzhou, Zhejiang, 310005, China.

Traditional Chinese Medical University, Hangzhou, Zhejiang, 310005, China; The Second Clinical Medical College of Zhejiang Traditional, Chinese Medical University, Hangzhou, Zhejiang, 310005, China; Pang Dexiang Famous Chinese Medical Studio of Zhejiang Province, Hangzhou, Zhejiang, 310005, China; Oncology Department of Xinhua Hospital in Zhejiang Province, Hangzhou, Zhejiang, 310005, China.

出版信息

Biomed Pharmacother. 2018 Sep;105:413-419. doi: 10.1016/j.biopha.2018.05.094. Epub 2018 Jun 2.

Abstract

Dysregulation of mircoRNAs (miRs) that act as tumor suppressors or oncogenes is participated in tumorigenesis and progression. The aim of the study is to investigate the role and mechanism of miR-1297 in gastric cancer (GC). Here, we demonstrated that miR-1297 expression was significantly lower in GC tissue samples compared to adjacent normal tissue samples in 62 cases GC patients. Lower miR-1297 expression positively associated with larger tumor size, lymph node metastasis, advanced TNM stage and poor survival time of patients. Upregulation of miR-1297 significantly inhibited cell proliferation and cell colony forming abilities in vitro. However, downregulation of miR-1297 can cause the reverse biological function changes. In vivo, miR-1297 overexpression suppressed tumor growth. Luciferase reporter assay showed that CREB1 was a direct target of miR-1297 in GC. MiR-1297 inhibited the expression of CREB1 by targeting the 3'UTR of CREB1. Additionally, we demonstrated that CREB1 overexpression rescued the effects on GC cell growth induced by miR-1297. Therefore, these results indicated that miR-1297 might be a prognostic predictor for GC and potential target of GC treatment.

摘要

miRNAs(miRs)的失调作为肿瘤抑制因子或癌基因参与肿瘤的发生和发展。本研究旨在探讨 miR-1297 在胃癌(GC)中的作用和机制。在这里,我们证明了在 62 例 GC 患者中,miR-1297 的表达在 GC 组织样本中明显低于相邻正常组织样本。较低的 miR-1297 表达与较大的肿瘤大小、淋巴结转移、较晚的 TNM 分期和患者较差的生存时间呈正相关。miR-1297 的上调显著抑制了体外细胞增殖和细胞集落形成能力。然而,下调 miR-1297 会导致相反的生物学功能变化。在体内,miR-1297 的过表达抑制了肿瘤的生长。荧光素酶报告基因分析表明,CREB1 是 GC 中 miR-1297 的直接靶基因。miR-1297 通过靶向 CREB1 的 3'UTR 抑制 CREB1 的表达。此外,我们证明 CREB1 的过表达可以挽救 miR-1297 对 GC 细胞生长的影响。因此,这些结果表明,miR-1297 可能是 GC 的预后预测因子和 GC 治疗的潜在靶点。

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