Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gain- and loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain- and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

中文翻译：

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环状RNA hsa_circ_0000326充当miR-338-3p海绵，促进肺腺癌的进展

环状RNA（circRNA）是一类新型的非编码RNA，可在转录或转录后水平调节基因表达。根据最近的研究，circRNA参与了癌症的发病机制，但是circRNA在肺腺癌中的作用尚不清楚。在这项研究中，我们使用微阵列分析和qRT-PCR在人肺腺癌组织中鉴定了一种新型上调的circRNA，hsa_circ_0000326。然后，我们使用功能增强和丧失功能测定腺癌细胞中的hsa_circ_0000326的生物学作用。生物信息学数据库用于筛选潜在的靶标miRNA，萤光素酶报告基因检测和RNA-FISH进一步验证了相互作用。通过蛋白质印迹检测下游蛋白质。最后，我们在裸鼠中建立异种移植物，以评估体内hsa_circ_0000326的功能。我们发现hsa_circ_0000326的高表达与人类肺腺癌的肿瘤大小，区域淋巴结状态和分化程度相关。此外，我们进行了功能获得和功能丧失测定，发现hsa_circ_0000326充当细胞增殖和迁移的正调节剂，而凋亡是负调节剂。机理研究表明，hsa_circ_0000326充当miR-338-3p海绵并改变了miR-338-3p的功能，进而上调了下游靶标RAB14的表达并影响了肺腺癌细胞的增殖，迁移和凋亡。我们的研究结果共同揭示了hsa_circ_0000326在增殖中的关键作用，