环状RNA_100242作为竞争性内源RNA结合miR-145影响膀胱癌发生发展的机制研究

CircRNA can function as miRNA sponges and play an important role in the regulation of cancer initiation and development. However, the biological function and mechanism of circRNA in bladder cancer have remained poorly understood. In our previous study, we have demonstrated that circ_100242 has miR-145 binding sites. In bladder cancer tissues, circ_100242 is highly expressed and negatively correlated with miR-145. In addition, miR-145 could influence the biological behavior of bladder cancer cells. We propose the hypothesis that circ_100242 might contribute to bladder carcinogenesis by acting as a competitive endogenous RNA (ceRNA) against miR-145. To test this hypothesis, we will carry out experiments in bladder cancer cells. Through RNA interference and transfection of adenovirus vector plasmid, we aim to investigate the role of circ_100242 in bladder cancer from multiple levels of analysis, and determine the regulatory mechanism of circ_100242 on biological activity of bladder cancer cells by decoying miR-145. This project will help to elucidate the mechanism of bladder cancer from a new perspective of circ_100242, which provides new ideas for improving outcomes of bladder cancer.

环状RNA可作为miRNA海绵在肿瘤发生发展中发挥重要的调控作用。迄今对环状RNA在膀胱癌中的生物学功能及作用机制仍知之甚少。申请人前期研究发现，环状RNA_100242（circ_100242）在膀胱癌组织中表达上调，它具有miR-145的结合位点，并与miR-145的表达呈负相关；而miR-145可影响膀胱癌细胞的生物学行为。因此，申请人提出假说：circ_100242可能作为竞争性内源RNA（ceRNA）结合miR-145影响膀胱癌发生发展。为验证这一假说，我们将采用RNA干扰和腺病毒载体转染等手段，从细胞和分子水平深入探讨circ_100242在膀胱癌发生发展中的重要作用，明确circ_100242通过miR-145调控膀胱癌细胞生物学行为的机制。本研究将从circ_100242这个新视点为揭示膀胱癌的发生机制奠定基础，为提高膀胱癌的治疗效果提供新的思路。

环状RNA可作为miRNA海绵在肿瘤发生发展中发挥重要的调控作用。迄今对环状RNA在膀胱癌中的生物学功能及作用机制仍知之甚少。申请人前期研究发现，环状RNA_100242（circ_100242）在膀胱癌组织中表达上调，它具有miR-145的结合位点，并与miR-145的表达呈负相关；而miR-145可影响膀胱癌细胞的生物学行为。因此，申请人提出假说：circ_100242可能作为竞争性内源RNA（ceRNA）结合miR-145影响膀胱癌发生发展。本研究首先通过 circ_100242 腺病毒载体上调膀胱癌细胞 circ_100242 的表达水平，发现能促进膀胱癌细胞的增殖和迁移；通过siRNA 转染下调膀胱癌细胞 circ_100242 的表达水平，发现能抑制膀胱癌细胞的增殖和迁移。然后，采用 RNA 结合蛋白免疫沉淀（RIP）和RNA 荧光原位杂交（FISH），证实 circ_100242可能作为竞争性内源 RNA 结合 miR-145。本研究从circ_100242这个新视点为揭示膀胱癌的发生机制奠定基础，为提高膀胱癌的治疗效果提供新的思路。