Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey.
Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey.
Prostate Cancer Prostatic Dis. 2021 Sep;24(3):891-902. doi: 10.1038/s41391-021-00353-0. Epub 2021 Mar 22.
Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancer in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells.
We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models.
In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway.
In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.
在发达国家，前列腺癌（PCa）是继肺癌之后男性中最常见的恶性肿瘤。为了开发更好的治疗策略并揭示更有效的治疗靶点，迫切需要研究 PCa 的潜在分子机制。在这项研究中，我们旨在探索 CASC11 与 miR-145 和 IGF1R 之间在 PCa 细胞恶性进展过程中的潜在功能。
我们首先研究了 CASC 基因家族中非编码成员的致癌潜力，并分析了 CASC11 过表达对 DU145、LNCaP 和 PC3 PCa 细胞增殖、迁移和集落形成能力的影响。然后，我们在体外模型中探索了 CASC11、miR-145 和 IGF1R 表达的相关性及其对 PI3K/AKT/mTOR 信号通路的影响。
计算机分析显示，在 CASC 家族中，只有 CASC11 表现出一致的结果，考虑到其差异表达及其与患者总生存率的关系。我们证明，CASC11 的异位过表达显著增加了这三种细胞系的增殖、集落形成和迁移能力。CASC11 过表达导致 miR-145 抑制和 IGF1R 过表达，从而激活 PI3K/AKT/mTOR 信号通路。
总之，我们发现与相应对照相比，CASC11 在 PCa 细胞和临床肿瘤样本中上调，并揭示了异位 CASC11 过表达通过 CASC11/miR-145/IGF1R 轴促进与 PCa 进展相关的细胞表型。
