• Oxygenases
• Targeted therapy
• Tumor metastasis

• colon cancer
• metastasis
• occludin
• p38 MAPK
• prolyl hydroxylase 3

• Humans
• Prolyl Hydroxylases
• Occludin/genetics
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Procollagen-Proline Dioxygenase
• Rectal Neoplasms
• p38 Mitogen-Activated Protein Kinases/metabolism

• Energy metabolism
• Gastrointestinal neoplasms
• Glycolysis
• Hypoxia
• Mitochondria
• Oxidative phosphorylation

• Humans
• Gastrointestinal Neoplasms/drug therapy
• Carcinogenesis
• Cell Transformation, Neoplastic
• Hypoxia
• Energy Metabolism

• Cancer
• Hypoxia-inducible factor
• Proline hydroxylation
• Prolyl hydroxylase

Clear cell renal cell carcinoma (ccRCC) is one of the main subtypes of renal cell carcinoma, with intense aggressiveness. The involvement of circular RNAs (circRNAs) in human cancers attracts much concern. The intention of this study was to investigate the expression of circ_101341 and explore its function in ccRCC.

The expression of circ_101341, miR-411 and Egl nine homolog 3 (EGLN3) was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were monitored by transwell assay. Xenograft model was established to explore the role of circ_101341 in vivo. The protein levels of E-cadherin (E-cad), N-cadherin (N-cad), matrix metalloprotein-9 (MMP9) and EGLN3 were detected by Western blot. Bioinformatic analysis was conducted using Circinteractome and starBase. The targeted relationship was verified using dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA pull-down assay.

The expression of circ_101341 was elevated in ccRCC tissues and cells. Functionally, circ_101341 knockdown depleted proliferation, migration and invasion of ccRCC cells in vitro and restricted tumor growth in vivo. Circ_101341 directly targeted miR-411, and miR-411 inhibition revised the inhibitory effects of circ_101341 knockdown on proliferation, migration and invasion in ccRCC cells. Moreover, miR-411 directly bound to EGLN3, and EGLN3 overexpression also rescued the effects of circ_101341 knockdown.

Circ_101341 functioned as a tumor promoter to strengthen proliferation, migration and invasion by regulating EGLN3 via sponging miR-411, indicating that circ_101341 was a potential diagnostic and therapeutic biomarker of ccRCC.

• EGN3
• ccRCC
• circ_101341
• miR-411

The aim of this study was to determine the suitability of serum prolyl hydroxylase-3 (PHD3) as a diagnostic or monitoring biomarker of renal cell carcinoma (RCC).

Between October 2013 and March 2015, we prospectively recruited study participants. The RCC group consisted of 56 patients who underwent radical or partial nephrectomy. The control group included 56 healthy kidney donors and 13 patients with benign renal masses. Blood from the RCC patients was sampled prior to surgery and again 1 and 3 months after the operation. Serum PHD3 levels were measured via enzyme-linked immunosorbent assay and compared between RCC patients and controls.

RCC patients had higher serum PHD3 levels than controls (0.79±0.17 ng/mL vs. 0.73±0.09 ng/mL, p=0.023), with an area under curve (AUC) of 0.668. With a cutoff value of 0.761 ng/ml, the sensitivity, specificity, positive predictive value, and negative predictive value were 66.1%, 68.1%, 28.8%, and 37.3%, respectively. No significant difference in PHD3 level was observed between healthy kidney donors and patients with benign renal masses. The predictive performance of PHD3 was improved in subgroup analyses of RCC patients with a tumor size >2 cm (n=40) or clear-cell histology (n=44), with AUCs of 0.709 and 0.688, respectively. Among 37 patients with PHD3 levels greater than the cutoff value of 0.761 ng/mL, the postoperative PHD3 levels at 1 and 3 months were significantly lower than the preoperative PHD3 levels (both p<0.001).

Serum PHD3 represents a novel RCC biomarker that shows acceptable diagnostic performance.

• Area under curve
• Carcinoma, renal cell
• Early diagnosis
• Nephrectomy

• cancer stem cells
• colon cancer
• mouse double minute 2 homolog (MDM2)
• p53
• prolyl hydroxylase 3
• protein stability

• apoptosis
• hepatocellular carcinoma
• hypoxia-inducible factor 2α
• prognosis
• prolyl hydroxylase 3

Hypoxia-inducible factors (HIFs) are key regulators in oxygen homeostasis. Their stabilization and activity are regulated by prolyl hydroxylase domain (PHD)-1, -2, -3 and factor inhibiting HIF (FIH). This study investigated the relation between these oxygen sensors and the clinical behaviors and prognosis of hepatocellular carcinoma (HCC). Tissue microarray and RT-PCR analysis of tumor tissues and adjacent non-tumor liver tissues revealed that mRNA and protein levels of both PHD3 and FIH were lower within tumors. The lower expression of PHD3 in tumor was associated with larger tumor size, incomplete tumor encapsulation, vascular invasion and higher Ki-67 LI (p < 0.05). The lower expression of FIH in tumor was associated with incomplete tumor encapsulation, vascular invasion, as well as higher TNM stage, BCLC stage, microvascular density and Ki-67 LI (p < 0.05). Patients with reduced expression of PHD3 or FIH had markedly shorter disease-free survival (DFS), lower overall survival (OS), or higher recurrence (p < 0.05), especially early recurrence. Patients with simultaneously reduced expression of PHD3 and FIH exhibited the least chance of forming tumor encapsulation, highest TNM stage (p < 0.0083), lowest OS and highest recurrence rate (p < 0.05). Multivariate analysis indicated that a lower expression of FIH independently predicted a poor prognosis in HCC. These findings indicate that downregulation of PHD3 and FIH in HCC is associated with more aggressive tumor behavior and a poor prognosis. PHD3 and FIH may be potential therapeutic targets for HCC treatment.

• asparaginyl hydroxylase factor inhibiting HIF-1
• hepatocellular carcinoma
• hypoxia-inducible factors
• prognostic factor
• prolyl hydroxylase domain-containing proteins