Yin Cong, Liufu Cen, Ye Shuai, Zhu Tao, Jiang Jiahao, Wang Mingxia, Zhou Liqun, Yao Lin, Wang Yan, Shi Bentao
Department of Urology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, No. 3002, Sungangxi Road, Shenzhen, 518035, People's Republic of China.
Shenzhen University Health Science Center, Shenzhen, 518055, China.
Cell Mol Biol Lett. 2025 Feb 16;30(1):20. doi: 10.1186/s11658-025-00687-w.
Recent studies have illuminated the complexities of treating advanced bladder cancer (BCa), underscoring the importance of comprehending its molecular mechanisms for creating novel therapies. While the role of Karyopherin a2 (KPNA2) in promoting BCa growth is established, the precise mechanism remains elusive.
To investigate the regulatory role of KPNA2 in BCa, we employed a comprehensive approach integrating clinical case data and bioinformatics analysis to evaluate the expression of KPNA2 in BCa tissues. Mechanisms promoting cancer by KPNA2 were examined using both in vivo and in vitro models.
Our research reveals that miR-26b-5p acts as an anticancer factor by targeting and inhibiting KPNA2 expression. Furthermore, we have observed that the interaction between KPNA2 and Kinesin Family Member C1 (KIFC1) facilitates the transition of BCa cells into the G2/M phase, thereby promoting tumor advancement via activation of the Phosphoinositide 3-kinase (PI3K)- Protein Kinase B (AKT) pathway. Importantly, this investigation is the first to identify KPNA2 expression in exosomes originating from BCa tissues. Plasma exosomes from patients with BCa exhibited notably increased levels of KPNA2 compared with healthy controls, suggesting KPNA2 as a potential new tumor indicator. Additionally, KPNA2 from BCa cells triggered the conversion of fibroblasts into cancer-associated fibroblasts (CAFs), which secreted elevated levels of interleukin-6 (IL-6), contributing to a tumor-supporting environment.
These findings suggest that KPNA2 is a key gene that promotes BCa progression, can potentially be a novel tumor marker, and may serve as a new therapeutic target for BCa.
近期研究揭示了晚期膀胱癌（BCa）治疗的复杂性，强调了理解其分子机制以开发新疗法的重要性。虽然核转运蛋白α2（KPNA2）在促进BCa生长中的作用已得到证实，但其确切机制仍不清楚。
为了研究KPNA2在BCa中的调控作用，我们采用了综合方法，整合临床病例数据和生物信息学分析来评估KPNA2在BCa组织中的表达。使用体内和体外模型研究KPNA2促进癌症的机制。
我们的研究表明，miR-26b-5p通过靶向和抑制KPNA2表达发挥抗癌因子的作用。此外，我们观察到KPNA2与驱动蛋白家族成员C1（KIFC1）之间的相互作用促进了BCa细胞向G2/M期的转变，从而通过激活磷脂酰肌醇3激酶（PI3K）-蛋白激酶B（AKT）途径促进肿瘤进展。重要的是，这项研究首次鉴定了源自BCa组织的外泌体中的KPNA2表达。与健康对照相比，BCa患者的血浆外泌体中KPNA2水平显著升高，表明KPNA2是一种潜在的新肿瘤指标。此外，BCa细胞中的KPNA2触发成纤维细胞转化为癌症相关成纤维细胞（CAF），后者分泌升高水平的白细胞介素-6（IL-6），有助于形成肿瘤支持环境。
这些发现表明，KPNA2是促进BCa进展的关键基因，可能是一种新的肿瘤标志物，并可能成为BCa的新治疗靶点。
