Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer and is associated with high recurrence, poor treatment, and low survival rates. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates the response to hypoxia, a major factor in the tumor microenvironment that affects tumor development and progression in various cancer types. However, microRNA (miRNA) sequence analysis revealed that only a few miRNAs targeting HIF-1α had been discovered. In the present study, we investigated HIF-1α expression in OSCC and the effect of HIF-1α-targeting miRNAs on the progression and metastatic potential of OSCC. We analyzed public databases to explore which miRNAs target HIF-1α expression. In addition, the expression of proteins involved in the cell cycle, proliferation, and apoptosis in HSC-2 cells was analyzed after miRNA-126 mimic treatment. Furthermore, to investigate the effect of miRNA-126 on the proliferation and invasion ability of OSCC cells, 5-ethynyl-2′-deoxyuridine and Transwell assays were performed. The activities of MMP-2 and MMP-9 were evaluated via gelatin zymography. Our results showed that miRNA-126, which targets HIF-1α, enhances OSCC cell proliferation by regulating the cell cycle and reinforces the cell mobility of OSCC via HIF-1α expression. These findings suggest that miRNA-126 may be a novel marker for OSCC treatment and the development of new tools for patients with OSCC.

정신분열은 대표적인 신경정신성 질환으로 정신분열 환자들은 정신적, 감정적 및 행동적인 장애로 인해 고통받고 있다. 이 연구는 흰쥐를 대상으로 정신분열을 유도함으로써 골격근 조직에서 반응하는 혈관생성 관련 단백질의 변화를 살펴보고 규칙적인 운동의 효과를 알아보고자 수행되었다. 연구의 목적을 위해 흰쥐(SD rats) 총 18마리를 통제(n=6), 정신분열(n=6), 정신분열+운동(n=6) 집단으로 구분하였다. 정신분열 및 정신분열+운동 집단은 총 2주 동안 MK-801처치를 통해 정신분열을 유도하였으며, 정신분열+운동 집단은 4주간 규칙적인 유산소성 운동을 수행하였다. 유산소성 운동은 실험동물용 트레드밀을 이용하여 수행되었으며 HIF-1α 및 VEGF 단백질은 western blot을 통해 관찰하였다. 연구결과, HIF-1α 단백질은 집단간 차이를 보이지 않았다(p>.05). VEGF 단백질의 경우, 통제집단보다 정신 분열 집단에서 유의하게 낮게 나타났으며(p<.01), 정신분열+운동 집단의 VEGF가 정신분열 집단보다 유의하게 높게 나타났다(p<.01). 따라서 골격근 내 혈관생성 관련 단백질들은 정신분열 유도에 의해 낮아질 수 있으며 반대로 운동은 이를 개선하는 효과를 가지는 것으로 사료된다.

The mechanisms underlying the actions of the antioxidants upon reactive oxygen species (ROS) generation by NADPH oxidase complex have remained uncertain. In this study, we investigated NADPH oxidase activity and the role of antioxidant enzymes upon the generation of ROS during hypoxic stress. ROS generation was found to increase in the mouse kidney under hypoxic stress in a time-dependent manner. Moreover, we found in MCT cells that hypoxia-induced hydrogen peroxide production was decreased by NAC pretreatment. We further analyzed HIF-1α, PHD2 and VHL expression in the NAC-pretreated MCT cells and assessed the response of antioxidant enzymes at the transcriptional and translational levels. SOD3 and Prdx2 were significantly increased during hypoxia in the mouse kidney. We also confirmed in hypoxic Prdx2-l- and SOD3 transgenic mice that erythropoietin (EPO) is transcriptionally regulated by HIF-1α. In addition, although EPO protein was found to be expressed in a HIF-1α independent manner in three mouse lines, its activity differed markedly between normal and Prdx2-l-/SOD3 transgenic mice during hypoxic stress. In conclusion, our current results indicate that NADPH oxidase-mediated ROS generation is associated with hypoxic stress in the mouse kidney and that SOD3 and Prdx2 cooperate to regulate cellular redox reactions during hypoxia.

Epigallocatechin-3-gallate (EGCG) and theaflavins (TF) are polyphenols included in green and black teas, respectively. Both green and black teas have been studied for their potential health benefits for cancer. Hypoxia-inducible factor (HIF) has been implicated multiple physiological and pathophysiological pathways, particularly, oncogenesis. But, the molecular pathways that govern the cell response to EGCG are not fully elucidated. The present study investigated the intracellular mechanism in oral squamous cell carcinoma (OSCC) cells treated with EGCG, focusing on HIF-1 expression and its effect on epithelial phenotype. EGCG decreased phosphorylated Raf-1 protein in YD 8 OSCC cell, but B-raf protein was not affected at all by EGCG and TF. In addition, we here found that EGCG regulated HIF-1α expression independent of Raf-1 protein. Taken together with our previous result, the result imply that EGCG is attributed to the HIF-1α expression via Raf/MEK/ERK pathway, and the HIF-1α expression is associated with the change of epithelial phenotype in OSCC cell.