Yunjie Wang

UCP2 Inhibits ROS-Mediated Apoptosis in A549 under Hypoxic Conditions

The Crosstalk between a tumor and its hypoxic microenvironment has become increasingly important. However, the exact role of UCP2 function in cancer cells under hypoxia remains unknown. In this study, UCP2 showed anti-apoptotic properties in A549 cells under hypoxic conditions. Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS) accumulation (P<0.001) and apoptosis (P<0.001) compared to the controls when the cells were exposed to hypoxia. Moreover, over-expression of UCP2 inhibited the release of cytochrome C and reduced the activation of caspase-9. Conversely, suppression of UCP2 resulted in the ROS generation (P = 0.006), the induction of apoptosis (P<0.001), and the release of cytochrome C from mitochondria to the cytosolic fraction, thus activating caspase-9. These data suggest that over-expression of UCP2 has anti-apoptotic properties by inhibiting ROS-mediated apoptosis in A549 cells under hypoxic conditions.

Intraoperative recurrent laryngeal nerve monitoring: a useful method for patients with esophageal cancer

It is well accepted that recurrent laryngeal nerve paralysis is a severe complication of esophagectomy or lymphadenectomy performed adjacent to the recurrent laryngeal nerves. Herein, determination of the effectiveness of implementing continuous recurrent laryngeal nerve monitoring to reduce the incidence of recurrent laryngeal nerve paralysis after esophagectomy was sought. A total of 115 patients diagnosed with esophageal cancer were enrolled in the thoracic section of the Tangdu Hospital of the Fourth Military Medical University from April 2008 to April 2009. Clinical parameters of patients, the morbidity, and the mortality following esophageal resection were recorded and compared. After the surgery, a 2-year follow up was completed. It was found that recurrent laryngeal nerve paralysis and postoperative pneumonia were more frequently diagnosed in the patients that did not receive continuous recurrent laryngeal nerve monitoring (6/61 vs. 0/54). Furthermore, positive mediastinal lymph nodes (P = 0.015), total mediastinal lymph nodes (P < 0.001), positive total lymph nodes (P = 0.027), and total lymph nodes (P < 0.001) were more often surgically removed in the patients with continuous recurrent laryngeal nerve monitoring. These patients also had a higher 2-year survival rate (P = 0.038) after surgery. It was concluded that continuous intraoperative recurrent laryngeal nerve monitoring is technically safe and effectively identifies the recurrent laryngeal nerves. This may be a helpful method for decreasing the incidence of recurrent laryngeal nerve paralysis and postoperative pneumonia, and for improving the efficiency of lymphadenectomy.

TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway

BACKGROUND The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway. MATERIALS AND METHODS The expression of TC-1 was immunohistochemically examined in 147 patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level. RESULTS TC-1 was detected in 97 of the 147 non-small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P < 0.01). In vitro experiments demonstrated that TC-1 expression affected both proliferation and invasion in the A549 cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathways downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level. CONCLUSIONS TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors.

TC-1 overexpression promotes cell proliferation in human non-small cell lung cancer that can be inhibited by PD173074.

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC.

Identification of GIRK2-4 subunits in human esophageal smooth muscle cells.

Acetylcholine (ACh) secreted from the vagus nerve contributes to the physiological and pathological regulation of the contraction and relaxation of human esophageal smooth muscle. Expression of acetylcholine-sensitive G protein‑activated inwardly rectifying potassium channels (GIRKs) occurs widely in the heart, nervous system and gastrointestine, but the role of GIRKs in the esophagus remains unclear. In the present study, expression of the GIRK1-4 subunits in mRNA and total protein was examined in human esophageal smooth muscle cells (SMCs) by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. mRNA and protein expression of the GIRK2-4 subunits was detected in human esophageal longitudinal muscle (LM) and circular muscle (CM) cells. However, GIRK1 mRNA and protein were not observed in either the esophageal LM or CM. This study is the first to identify the expression of GIRK2-4 subunits in human esophageal SMCs.