The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16–25)) in BCa and to consider the opportunity of using circSTAG2(16–25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16–25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16–25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16–25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16–25) activity, we confirmed that circSTAG2(16–25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16–25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16–25) might be considered as a potential biomarker for recurrence prediction.
本研究旨在阐明环状RNA hsa_circ_0139697（circSTAG2(16–25)）在膀胱癌中的调控机制，并探讨从膀胱癌患者尿液中分离的circSTAG2(16–25)作为疾病进展预测标志物的可能性。该环状RNA的选择基于其亲本基因STAG2在膀胱癌生物学中的特殊作用。从25个STAG2来源的环状RNA中筛选出hsa_circ_0139697，因其在膀胱癌患者与健康志愿者尿液中的表达存在差异。在肿瘤复发患者的尿液样本中检测到更高水平的circSTAG2(16–25)。同时，在致瘤性更强的膀胱癌细胞系中也观察到circSTAG2(16–25)的高表达。过表达circSTAG2(16–25)可促进膀胱癌细胞的增殖、迁移和侵袭能力。为探究其作用机制，我们通过生物信息学预测并体外验证了circSTAG2(16–25)能够结合miR-145-5p。研究表明miR-145-5p可抑制多个促进膀胱癌进展的基因，其中TAGLN2基因编码的Transgelin 2蛋白在膀胱癌细胞迁移和侵袭过程中发挥重要作用。因此，circSTAG2(16–25)可能通过吸附肿瘤抑制因子miR-145-5p，进而激活TAGLN2的表达。此外，circSTAG2(16–25)有望成为预测膀胱癌复发的潜在生物标志物。
肿瘤(癌症)患者之家