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Background <p>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 (<i>KPNA2</i>) in promoting BCa growth is established, the precise mechanism remains elusive.</p> Methods <p>To investigate the regulatory role of <i>KPNA2</i> in BCa, we employed a comprehensive approach integrating clinical case data and bioinformatics analysis to evaluate the expression of <i>KPNA2</i> in BCa tissues. Mechanisms promoting cancer by <i>KPNA2</i> were examined using both in vivo and in vitro models.</p> Results <p>Our research reveals that miR-26b-5p acts as an anticancer factor by targeting and inhibiting <i>KPNA2</i> expression. Furthermore, we have observed that the interaction between <i>KPNA2</i> and Kinesin Family Member C1 (<i>KIFC1</i>) 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 <i>KPNA2</i> expression in exosomes originating from BCa tissues. Plasma exosomes from patients with BCa exhibited notably increased levels of <i>KPNA2</i> compared with healthy controls, suggesting <i>KPNA2</i> as a potential new tumor indicator. Additionally, <i>KPNA2</i> 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.</p> Conclusions <p>These findings suggest that <i>KPNA2</i> 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.</p> Graphical Abstract <p></p>

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Tumor-derived exosomal KPNA2 activates fibroblasts and interacts with KIFC1 to promote bladder cancer progression, a process inhibited by miR-26b-5p

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月16日

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  • Cong Yin,
  • Cen Liufu,
  • Shuai Ye,
  • Tao Zhu,
  • Jiahao Jiang,
  • Mingxia Wang,
  • Liqun Zhou,
  • Lin Yao,
  • Yan Wang,
  • Bentao Shi

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Graphical Abstract