Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3), also known as lysyl hydroxylase 3 (LH3) has been demonstrated to be overexpressed in several kinds of cancers and facilitate cell migration. Currently, we aimed to reveal the role of PLOD3 in renal cell carcinoma (RCC) progression, and explore whether TWIST1 (Twist family bHLH transcription factor 1) is involved in this process. Fifty-eight paired RCC tissues and normal tissues were collected and subjected to qPCR and immunohistochemistry (IHC) technology to detect the expression levels of PLOD3. The clinical value of PLOD3 in predicting RCC progression was then explored. Cell-Counting Kit-8 (CCK-8), wound healing, transwell chambers and tumor-bearing experiments were applied to monitor cell proliferation, migration, invasion and tumorigenesis. Protein levels were determined by using western blotting technology to assess cell apoptosis and epithelial to mesenchymal transition (EMT). PLOD3 expression was enhanced in RCC tissues and cells, which predicted higher T (tumor), N (lymph node) and M (metastasis) stages, histological grade and TNM (tumor, lymph node, metastasis) stage. PLOD3 downregulation in RCC A498 cells obviously inhibited cell proliferation, migration, invasion, EMT and tumorigenesis and increased cell apoptosis. PLOD3 overexpression led to opposite results in RCC A704 cells. PLOD3 downregulation reduced the expression levels of TWIST1, β-catenin and p-AKT. In addition, TWIST1 overexpression rescued the repressions of cell proliferation, migration, invasion, EMT and the activation of β-catenin and AKT signaling in addition to apoptosis promotion induced by PLOD3 downregulation. Collectively, this study illustrated that PLOD3 knockdown suppressed RCC malignance via inhibiting TWIST1-mediated activation of β-catenin and AKT signaling.

胶原蛋白赖氨酸，2-氧戊二酸5-二加氧酶（PLOD3），也称为赖氨酰羟化酶3（​​LH3）已被证明在几种癌症中过表达并促进细胞迁移。目前，我们旨在揭示PLOD3在肾细胞癌（RCC）进展中的作用，并探讨TWIST1（Twist家族bHLH转录因子1）是否参与此过程。收集58对RCC组织和正常组织，并进行qPCR和免疫组织化学（IHC）技术检测PLOD3的表达水平。然后探讨了PLOD3在预测RCC进展中的临床价值。Cell-Counting Kit-8（CCK-8），伤口愈合，transwell小室和荷瘤实验用于监测细胞增殖，迁移，侵袭和肿瘤发生。通过使用蛋白质印迹技术评估细胞凋亡和上皮向间质转化（EMT），确定蛋白质水平。在RCC组织和细胞中PLOD3表达增强，这预示着较高的T（肿瘤），N（淋巴结）和M（转移）阶段，组织学分级和TNM（肿瘤，淋巴结，转移）阶段。RCC A498细胞中PLOD3的下调明显抑制细胞增殖，迁移，侵袭，EMT和肿瘤发生，并增加细胞凋亡。PLOD3过表达在RCC A704细胞中产生相反的结果。PLOD3下调降低了TWIST1，β-catenin和p-AKT的表达水平。此外，TWIST1的过表达可以挽救细胞增殖，迁移，侵袭，EMT以及β-catenin和AKT信号的激活以及PLOD3下调诱导的凋亡促进作用。总体而言，这项研究表明PLOD3敲低通过抑制TWIST1介导的β-catenin激活和AKT信号传导抑制了RCC恶性肿瘤。