Department of Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Neoplasma. 2024 Jun;71(3):231-242. doi: 10.4149/neo_2024_230904N469. Epub 2024 May 17.
Pancreatic cancer (PAAD) is a fatal malignancy with a poor prognosis. The treatment strategies are quite limited and gemcitabine is the canonical one, which has been proven to improve the prognosis of PAAD patients. However, the treatment efficiency of gemcitabine is far from satisfactory and remains to be further improved. DEAD-Box Helicase 46 (DDX46) is a kind of RNA helicase, which promotes multiple cancers development. However, its role in PAAD is largely unknown. In the present study, we found DDX46 was highly expressed in PAAD tissues and correlated with poor prognosis. Knockdown of DDX46 repressed PAAD cell growth in vitro and in vivo and sensitized PAAD cells to gemcitabine treatment. Mechanically, DDX46 bound to JMJD6 and promoted JMJD6/CDK4 signaling pathway. Overexpression of JMJD6 reversed the anti-tumor function of DDX46 knockdown. Our study found a novel pathological mechanism of PAAD progression and provided a potential therapeutic target to improve gemcitabine efficiency.
胰腺癌（PAAD）是一种预后不良的致命恶性肿瘤。治疗策略相当有限，吉西他滨是经典药物，已被证明能改善 PAAD 患者的预后。然而，吉西他滨的治疗效果远不理想，仍有待进一步提高。DEAD-Box Helicase 46（DDX46）是一种 RNA 解旋酶，可促进多种癌症的发展。然而，其在 PAAD 中的作用尚不清楚。在本研究中，我们发现 DDX46 在 PAAD 组织中高表达，并与不良预后相关。DDX46 的敲低抑制了 PAAD 细胞的体外和体内生长，并使 PAAD 细胞对吉西他滨治疗敏感。机制上，DDX46 与 JMJD6 结合并促进 JMJD6/CDK4 信号通路。JMJD6 的过表达逆转了 DDX46 敲低的抗肿瘤功能。我们的研究发现了 PAAD 进展的新病理机制，并为提高吉西他滨效率提供了一个潜在的治疗靶点。
