环状RNA hsa_circ_0007294内源性竞争miR-155-5p调控靶基因APC 抑制甲状腺乳头状癌侵袭转移的作用研究

Papillary thyroid carcinoma (PTC) is one of the fastest growing malignant tumors in recent years. The invasion and metastasis are the most two important factors for poor prognosis of this disease. The further and extensive study on mechanisms will be of great theoretical and practical significance. Our previous study have found that the expression of the circular RNA hsa_circ_0007294 was significantly decreased in PTC tissues; moreover, overexpression of hsa_circ_0007294 in PTC cell lines inhibited the invasion and metastasis of PTC cells and regulated the expression of miR-155-5p. Based on this novel discovery and the bioinformatics analysis as well as literature reports, the applicant's research group proposed that hsa_circ_0007294 may sponge miR-155-5p to up-regulate the target APC gene, thereby affecting the Wnt/β-catenin pathway, leading to inhibition of PTC invasion and metastasis. This project may demonstrate the correlation and mutual regulation among hsa_circ_0007294, miR-155-5p and APC through clinical patient’s study with tissue sample/clinical data analysis as well as in vitro and in vivo experiments, and further reveal the molecular mechanism of hsa_circ_0007294 behind PTC invasion and metastasis. This project may provide a new target and evidence for PTC diagnosis and treatment.

甲状腺乳头状癌（PTC）是近年来发病率增长最快的恶性肿瘤之一，侵袭转移是造成PTC预后不良的最重要因素。申请人前期研究发现环状RNA hsa_circ_0007294在PTC组织中表达异常降低，而在PTC细胞系中过表达hsa_circ_0007294可抑制PTC细胞侵袭转移，并具有调控miR-155-5p表达的作用。以这一新发现为切入点，结合生物信息学分析和文献报道，申请人课题组提出hsa_circ_0007294可内源性竞争miR-155-5p上调靶基因APC，进而影响Wnt/β-catenin通路抑制PTC侵袭转移的科学假说。本项目拟通过临床样本分析和细胞、动物实验，证实hsa_circ_0007294、miR-155-5p及APC三者的表达相关性和相互调控作用，进一步揭示hsa_circ_0007294对PTC侵袭转移的分子机制，为PTC诊治提供新靶点和新思路。

环状 RNA在甲状腺乳头状癌（PTC）的肿瘤进展中至关重要。本研究旨在评估hsa_circ_0007294的生物学行为及其潜在机制。本研究中通过qRT-PCR检测hsa_circ_0007294、miR-155-5p和PIAS1/APC的表达水平，通过MTT和Transwell试验检测PTC细胞增殖、迁移和侵袭能力，通过western试验检测相关蛋白表达水平，Dual-luciferase分析评估miR-155-5p与靶蛋白的关系。本研究的结果表明在PTC组织中发现了hsa_circ_0007294的下调，hsa_circ_0007294可以抑制PTC细胞增殖、迁移和侵袭能力。miR-155-5p被确认为hsa_circ_0007294的下游蛋白，以调节PIAS1和APC。沉默PIAS1或APC基因可以挽救hsa_circ_0007294引起的效应。综上所述，hsa_circ_0007294 通过靶向调控miR-155-5p/PIAS1/APC轴抑制PTC侵袭转移，表明hsa_circ_0007294可能成为PTC的新型治疗靶点。