Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b
Upregulated circular RNA circ_0007534 indicates an unfavorable prognosis in pancreatic ductal adenocarcinoma and regulates cell proliferation, apoptosis, and invasion by sponging miR-625 and miR-892b
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DOI：
10.1002/jcb.27658
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Meng, Xin
中科院分区：
文献类型：
--
作者：
Hao, Liguo;Rong, Wei;Meng, Xin
环状rna （circRNAs）被认为是人类疾病的关键调控因子和某些类型恶性肿瘤的生物标志物，包括胰腺导管腺癌（PDAC）。最近，circ_0007534被鉴定为一种新的与癌症相关的circRNA。然而，其临床相关性、功能作用和机制尚未在PDAC中得到研究。本研究采用实时定量聚合酶链反应（RT-qPCR）检测circ_0007534在60对PDAC组织样本和不同细胞系中的表达。通过功能丧失和功能获得试验检测circ_0007534影响的细胞增殖、凋亡和转移特性。同时还进行了动物实验。荧光素酶报告基因实验揭示了circ_0007534的潜在机制。因此，circ_0007534不仅在PDAC组织中过表达，而且在一组PDAC细胞系中也过表达，并且这种过表达与肿瘤晚期和淋巴结阳性侵袭密切相关。此外，circ_0007534可被视为PDAC患者的独立预后因素。在功能测试方面，circ_0007534显著增加了PDAC细胞的增殖、迁移和侵袭潜能。Circ_0007534可部分通过Bcl-2/caspase-3途径抑制细胞凋亡。异种移植研究进一步证实了circ_0007534促进细胞生长的作用。机制上，miR-625和miR-892b被circ_0007534擦拭。circ_0007534的致癌功能部分依赖于其对miR-625和miR-892b的调控。总之，我们的研究阐明了一种新的环状rna，它在PDAC中具有致癌功能。
Circular RNAs (circRNAs) have been regarded as critical regulators of human diseases and biological markers in some types of malignancies, including pancreatic ductal adenocarcinoma (PDAC). Recently, circ_0007534 has been identified as a novel cancer-related circRNA. Nevertheless, its clinical relevance, functional roles, and mechanism have not been studied in PDAC. In the current study, real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of circ_0007534 in 60-paired PDAC tissue samples and different cell lines. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, and metastatic properties affected by circ_0007534. An animal study was also carried out. The luciferase reporter assay was performed to uncover the underlying mechanism of circ_0007534. As a result, circ_0007534 was overexpressed not only in PDAC tissues but also in a panel of PDAC cell lines, and this overexpression is closely associated with advanced tumor stage and positive lymph node invasion. In addition, circ_0007534 may be regarded as an independent prognostic factor for patients with PDAC. For the part of functional assays, circ_0007534 significantly increased cell proliferation, migratory, and invasive potential of PDAC cells. Circ_0007534 could inhibit cell apoptosis partly via a Bcl-2/caspase-3 pathway. The xenograft study further confirmed the cell growth promoting the role of circ_0007534. Mechanistically, miR-625 and miR-892b were sponged by circ_0007534. The oncogenic functions of circ_0007534 is partly dependent on its regulation of miR-625 and miR-892b. In conclusion, our study illuminates a novel circRNA that confers an oncogenic function in PDAC.