circIFT80 Functions as a ceRNA of miR-1236-3p to Promote Colorectal Cancer Progression
circIFT80 Functions as a ceRNA of miR-1236-3p to Promote Colorectal Cancer Progression
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DOI：
10.1016/j.omtn.2019.08.024
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发表时间：
2019-12-06
影响因子：
8.8
通讯作者：
Cui, Ge
中科院分区：
文献类型：
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作者：
Feng, Wenming;Gong, Hui;Cui, Ge
环状RNAs(CircRNAs)是新近发现的一种新的非编码RNAs，参与多种生物学过程，然而，CircRNAs与结直肠癌(CRC)相关的分子机制尚不清楚。在本研究中，我们试图探索外体CircRNAs在结直肠癌进展中的作用。我们首先比较了结直肠癌患者和健康对照血浆外体CircRNA的表达模式。我们在结直肠癌血浆中发现了448个显著异常的外体CircRNA。我们重点研究了HSA_CIRC_0067835，它位于第3染色体上，起源于IFT80；因此，我们将其命名为大约IFT80。采用定量逆转录聚合酶链式反应(qRT-PCR)检测58例大肠癌组织和细胞系中CircIFT80的表达。通过功能分析评价了CircIFT80在体内外对肿瘤生长的影响。通过荧光素酶报告基因分析，证实了CircIFT80与miR-1236-3p之间的关系。我们发现，与正常对照组相比，在结直肠癌血清外切体、结直肠癌组织和结直肠癌细胞系中，大约IFT80的表达显著上调。在体外和体内，沉默IFT80抑制了结直肠癌细胞的生长。我们进一步证明了CircIFT80/miR-1236-3p/HOXB7轴在调节结直肠癌进展中起重要作用。双荧光素酶报告系统验证了CircIFT80、miR-1236-3p和HOXB7之间的直接相互作用。Western印迹证实，抑制CircIFT80可降低HOXB7的表达，而miR-1236-3p抑制剂可减弱CircIFT80的抑制作用。综上所述，这些数据表明，CircIFT80是通过miR-1236-3p/HOXB7轴将CircRNAs与结直肠癌进展联系起来的中心成分。
Circular RNAs (circRNAs), a recently identified new member of non-coding RNAs, are demonstrated to participate in diverse biological processes; however, the molecular mechanisms that link circRNAs with colorectal cancer (CRC) are not well understood. In the present study, we attempted to explore the roles of the exosomal circRNAs on CRC progression. We first compared the expression patterns of exosomal circRNAs between the plasma of CRC patients and healthy controls. We identified 448 significantly dysregulated exosomal circRNAs in CRC plasma. We focused on hsa_circ_0067835, which is located on chromosome 3 and derived from IFT80; thus, we named it circIFT80. Then, the expression of circIFT80 was detected in 58 CRC tissues and cell lines by qRT-PCR. Functional assays were performed to evaluate the effects of circIFT80 on tumor growth in vitro and in vivo. The relationship between circIFT80 and miR-1236-3p was confirmed by luciferase reporter assay. We found that circIFT80 was significantly upregulated in CRC serum exosomes, CRC tissues, and CRC cell lines compared with normal control. Silencing circIFT80 suppressed CRC cell growth both in vitro and in vivo. We further demonstrated that circIFT80/miR-1236-3p/HOXB7 axis plays an important role in regulating CRC progression. Dual-luciferase reporter system validated the direct interaction of circIFT80, miR-1236-3p, and HOXB7. Western blot verified that inhibition of circIFT80 decreased HOXB7 expression, while a miR-1236-3p inhibitor attenuated the effect of inhibition of circIFT80. In conclusion, these data suggest that circIFT80 is a central component linking circRNAs to the progression of CRC via a miR-1236-3p/HOXB7 axis.