目的:探讨circ-SFMBT2对非小细胞肺癌(non-small cell lung cancer，NSCLC)细胞生物学行为的影响以及对miR-7-5p/ADAM10分子轴的调控作用。方法:采用qRT-PCR法与Western印迹法分别检测NSCLC与癌旁组织中circ-SFMBT2、miR-7-5p、ADAM10的表达量；用Pearson法分析circ-SFMBT2与miR-7-5p、以及miR-7-5p与ADAM10的相关性；体外培养人支气管上皮样细胞(human bronchial epithelial-like cells, HBE)与肺癌细胞系H1650、H460、A549、H1299。用CCK-8与EdU实验检测细胞的增殖能力。用平板克隆形成实验检测细胞的克隆形成能力。用流式细胞术检测细胞凋亡率。用Transwell小室实验检测细胞侵袭。用双荧光素酶报告实验检测circ-SFMBT2与miR-7-5p、以及miR-7-5p与ADAM10的靶向关系。用裸鼠移植瘤实验检测敲低circ-SFMBT2对移植瘤生长的影响。用免疫组化实验检测移植瘤组织中ADAM10与Ki67蛋白阳性率。结果:circ-SFMBT2与ADAM10在NSCLC组织及细胞系中表达升高，而miR-7-5p的表达降低，circ-SFMBT2与miR-7-5p的表达呈负相关，而miR-7-5p与ADAM10的表达呈负相关。沉默circ-SFMBT2及miR-7-5p过表达可抑制细胞增殖、克隆形成及侵袭，还可促进其凋亡。circ-SFMBT2可靶向调控miR-7-5p，而ADAM10是miR-7-5p的靶基因。沉默circ-SFMBT2与抑制miR-7-5p联合作用，以及miR-7-5p过表达与ADAM10过表达联合作用均可促进细胞增殖、克隆形成及侵袭，并抑制其凋亡。沉默circ-SFMBT2可抑制移植瘤的生长。结论:沉默circ-SFMBT2可通过调控miR-7-5p/ADAM10分子轴而减弱NSCLC细胞增殖、克隆形成、侵袭能力并诱导其凋亡。

目的 探讨环状RNA(circRNA)SFMBT2(circ-SFMBT2)通过miR-224-5p/USP3轴对肝癌细胞增殖及迁移能力的影响.方法 选取人肝癌细胞株HepG2、SMMC7721、Huh-7、Sk-Hep-1及人正常肝细胞株LO2,采用实时荧光定量聚合酶链式反应(qRT-PCR)技术检测circ-SFMBT2在5个细胞株中的表达,筛选出高表达circ-SFMBT2的人肝癌细胞株HepG2和正常肝细胞株LO2进行后续实验,采用原位杂交实验检测circ-SFMBT2在HepG2和LO2中的亚细胞定位;选取人肝癌细胞系HepG2传代培养,利用Lipofectamine 2000为转染试剂进行转染,分为circ-SFMBT2转染对照组(circ-SFMBT2 NC,NC组)、circ-SFMBT2干扰组(si-circ-SFMBT2组)、miR-224-5 p过表达组(mimic组)、USP3过表达组(si-circ-SFMBT2+USP3组)、miR-224-5 p干扰组(si-circ-SFMBT2+in-hibitor组)、miR-224-5p和USP3双过表达组(mimic+USP3组),分别采用细胞增殖(CCK-8)、克隆斑点形成及Transwell实验检测6组HepG2细胞增殖和迁移能力,采用双荧光素报告实验检测circ-SFMBT2、miR-224-5 p和USP3在HepG2细胞中彼此之间的靶向关系.结果 qRT-PCR结果显示与正常肝细胞LO2比较,circ-SFMBT2在4株肝癌细胞中高表达,差异有统计学意义(P<0.05);原位杂交实验证实circ-SFMBT2存在于细胞质中;细胞增殖(CCK-8、克隆斑点实验)和迁移实验(Transwell实验)检测发现,si-circ-SFMBT2组细胞增殖和迁移能力较NC组降低(P<0.05),mimic组增殖和迁移能力较si-circ-SFMBT2+inhibitor组降低(P<0.05),mimic+USP3组细胞增殖和迁移能力较mimic组升高(P<0.05);双荧光素实验证实miR-224-5p和USP3是circ-SFMBT2的下游靶点.结论 circ-SFMBT2通过miR-224-5 p/USP3轴参与了对肝癌细胞增殖和迁移的调控.

Circular RNAs (circRNAs), a class of endogenous RNA molecules, are produced by alternative splicing of precursor RNA and are covalently linked at the 5′ and 3′ ends. Recent studies have revealed that dysregulated circRNAs are closely related to the occurrence and progression of gastrointestinal malignancies. Accumulating evidence indicates that circRNAs, including circPVT1, circLARP4, circ-SFMBT2, cir-ITCH, circRNA_100782, circ_100395, circ-DONSON, hsa_circ_0001368, circNRIP1, circFAT1(e2), circCCDC66, circSMARCA5, circ-ZNF652, and circ_0030235 play important roles in the proliferation, differentiation, invasion, and metastasis of cancer cells through a variety of mechanisms, such as acting as microRNA sponges, interacting with RNA-binding proteins, regulating gene transcription and alternative splicing, and being translated into proteins. With the characteristics of high abundance, high stability, extensive functions, and certain tissue-, time- and disease-specific expressions, circRNAs are expected to provide novel perspectives for the diagnoses and treatments of gastrointestinal malignancies.