RNF185 is a RING finger domain-containing ubiquitin ligase implicated in ER-associated degradation. Prostate tumor patient data analysis revealed a negative correlation between RNF185 expression and prostate cancer progression and metastasis. Likewise, several prostate cancer cell lines exhibited greater migration and invasion capabilities in culture upon RNF185 depletion. Subcutaneous inoculation of mouse prostate cancer MPC3 cells stably expressing shRNA against RNF185 into mice resulted in larger tumors and more frequent lung metastases. RNA-sequencing and Ingenuity Pathway Analysis identified wound healing and cellular movement among the most significant pathways upregulated in RNF185-depleted, compared to control prostate cancer cells. Gene Set Enrichment Analyses performed in samples from patients harboring low RNF185 expression and in RNF185-depleted lines confirmed the deregulation of genes implicated in EMT. Among those, COL3A1 was identified as the primary mediator of RNF185’s ability to impact migration phenotypes. Correspondingly, enhanced migration and metastasis of RNF185 KD prostate cancer cells were attenuated upon co-inhibition of COL3A1. Our results identify RNF185 as a gatekeeper of prostate cancer metastasis, partly via its control of COL3A1 availability. Implications: RNF185 identified as novel marker for prostate cancer metastasis, through control of COL3A1 expression.

中文翻译：

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RNF185对COL3A1表达的控制限制了前列腺癌的迁移和转移潜力

RNF185 是一种含有环指结构域的泛素连接酶，参与 ER 相关降解。前列腺肿瘤患者数据分析显示RNF185表达与前列腺癌进展和转移之间呈负相关。同样，一些前列腺癌细胞系在 RNF185 耗尽后在培养物中表现出更强的迁移和侵袭能力。将稳定表达针对 RNF185 的 shRNA 的小鼠前列腺癌 MPC3 细胞皮下接种到小鼠体内，会导致更大的肿瘤和更频繁的肺转移。RNA 测序和 Ingenuity 通路分析发现，与对照前列腺癌细胞相比，RNF185 耗尽的细胞中伤口愈合和细胞运动是上调的最重要通路之一。对来自 RNF185 低表达患者和 RNF185 耗尽株系的样本进行的基因集富集分析证实了与 EMT 相关的基因的失调。其中，COL3A1 被确定为 RNF185 影响迁移表型能力的主要介质。相应地，RNF185 KD 前列腺癌细胞增强的迁移和转移在 COL3A1 的共同抑制下减弱。我们的结果确定 RNF185 是前列腺癌转移的看门人，部分是通过它对 COL3A1 可用性的控制。意义：RNF185 通过控制 COL3A1 表达被确定为前列腺癌转移的新标志物。