Department of Engineering Research Center of Peptide Drug Discovery and Development, Nanjing, P.R. China.
Department of State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P.R. China.
Clin Cancer Res. 2018 Jan 15;24(2):486-498. doi: 10.1158/1078-0432.CCR-17-1851. Epub 2017 Nov 3.
Emerging studies demonstrate that long noncoding RNAs (lncRNA) participate in the regulation of various cancers. In the current study, a novel has been identified and explored in esophageal squamous cell carcinoma (ESCC). To discover a new regulatory circuitry in which RNAs crosstalk with each other, the transcriptome of lncRNA-miRNA-mRNA from ESCC and adjacent nonmalignant specimens were analyzed using multiple microarrays and diverse bioinformatics platforms. The functional role and mechanism of a novel were further investigated by gain-of-function and loss-of-function assays and An ESCC biomarker panel, consisting of , , and , was validated by qRT-PCR and hybridization using samples from 148 patients. as an oncogene is highly expressed in ESCC tissues and cell lines, and promotes ESCC cell proliferation and metastasis. Mechanistically, promotes expression of transcription factor Snail1 by competitively binding , resulting in the epithelial-mesenchymal transition (EMT) cascade. Moreover, also induces FSCN1 expression by sponging and upregulation of mRNA-stabilizing protein HuR, which further promotes ESCC invasion cascades. We also discovered and validated a clinically applicable ESCC biomarker panel, consisting of , , and , that is significantly associated with overall survival and provides additional prognostic evidence for ESCC patients. As a novel regulator, plays an important role in ESCC cell proliferation and metastasis. The regulatory axis provides bona fide targets for anti-ESCC therapies. .
新兴研究表明,长非编码 RNA(lncRNA)参与了多种癌症的调控。在本研究中,我们在食管鳞状细胞癌(ESCC)中鉴定并探索了一种新型 lncRNA。为了发现一种新的调控回路,使 RNA 之间能够相互交流,我们使用多个微阵列和不同的生物信息学平台分析了 ESCC 和相邻非恶性标本中的 lncRNA-miRNA-mRNA 转录组。通过功能获得和功能丧失实验进一步研究了 novel 的功能作用和机制,并通过 qRT-PCR 和原位杂交验证了由 、 、和 组成的 ESCC 生物标志物面板,该面板使用了来自 148 名患者的样本。作为一种致癌基因,在 ESCC 组织和细胞系中高表达,并促进 ESCC 细胞的增殖和转移。从机制上讲,通过竞争性结合 来促进转录因子 Snail1 的表达,导致上皮间质转化(EMT)级联反应。此外,还通过海绵吸附 和上调 mRNA 稳定蛋白 HuR 来诱导 FSCN1 的表达,从而进一步促进 ESCC 侵袭级联反应。我们还发现并验证了一个临床适用的 ESCC 生物标志物面板,由 、 、和 组成,与总生存期显著相关,并为 ESCC 患者提供了额外的预后证据。作为一种新型调节剂,在 ESCC 细胞的增殖和转移中发挥重要作用。该 调控轴为抗 ESCC 治疗提供了真正的靶点。