Department of Urology, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, The Second Hospital of Lanzhou University, Lanzhou, China.
Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, China.
Mol Carcinog. 2022 Jul;61(7):690-701. doi: 10.1002/mc.23411. Epub 2022 Apr 26.
Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) is a highly conserved member of aldehyde dehydrogenase (ALDHs) family. Recent studies reveal that it broadly involved in tumorigenesis and drug metabolism in kinds of cancer. However, the critical role of ALDH6A1 in bladder cancer progression and cisplatin resistance of cancer cells are still poorly understood. In this study, we researched the significant function of ALDH6A1 in bladder cancer. Our results showed that ALDH6A1 exhibited a decreased expression in clinical bladder cancer tissues and bladder cancer cell lines. Stable ALDH6A1 knockdown not only could promote cell growth and colony formation in bladder cancer cells, but also enhance drug resistance to cisplatin treatment. On the contrary, we found the active transcript factor hepatocyte nuclear factor 4α (HNF4α, NR2A1) by alveriene could upregulate ALDH6A1 expression, significantly inhibit the cell growth and colony formation of bladder cancer cells, and improve cisplatin sensitivity of bladder cancer cells. Together, our results show that ALDH6A1 plays as a tumor suppressor in bladder cancer, which regulated by HNF4a. ALDH6A1 could be a promising diagnostic marker and treatment target in bladder cancer.
醛脱氢酶 6 家族成员 A1（ALDH6A1）是醛脱氢酶（ALDHs）家族中高度保守的成员。最近的研究表明，它广泛参与各种癌症的肿瘤发生和药物代谢。然而，ALDH6A1 在膀胱癌进展和癌细胞对顺铂耐药中的关键作用仍知之甚少。在这项研究中，我们研究了 ALDH6A1 在膀胱癌中的重要功能。我们的结果表明，ALDH6A1 在临床膀胱癌组织和膀胱癌细胞系中表达下调。稳定的 ALDH6A1 敲低不仅可以促进膀胱癌细胞的生长和集落形成，还可以增强对顺铂治疗的耐药性。相反，我们发现姜黄素可以激活转录因子肝细胞核因子 4α（HNF4α，NR2A1），从而上调 ALDH6A1 的表达，显著抑制膀胱癌细胞的生长和集落形成，并提高膀胱癌细胞对顺铂的敏感性。总之，我们的结果表明，ALDH6A1 在膀胱癌中作为肿瘤抑制因子发挥作用，其受 HNF4a 调节。ALDH6A1 可能是膀胱癌有前途的诊断标志物和治疗靶点。
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