Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ), a phospholipid kinase generating PIP2, is positively expressed in breast cancer tissues, which correlates intimately with the progression of patients. However, little is known about the expression level of PIPKIγ in patients with other cancer types as well as their underlying regulation mechanisms. Here, we report that PIPKIγ is highly expressed in lung cancer tissues and its expression level is critical for lung cancer cell proliferation, which may serve as a prognostic marker for lung cancer patients. Meanwhile, we show that E3 ubiquitin ligase Smurf1 directly interacts with PIPKIγ and targets PIPKIγ for ubiquitination and degradation in lung cancer cells. Also, we discover that Smurf1 directly binds to the kinase domain of PIPKIγ via its C2 domain while Lysine 255 in PIPKIγ acts as the major ubiquitin acceptor site for Smurf1. In addition, we demonstrate that the phosphorylation mimicking mutant of Smurf1, Smurf1 T306D, prevents PIPKIγi2 from ubiquitination and subsequent degradation similar to the effect of forskolin-potentiated cAMP formation, suggesting that Thr306 in Smurf1 is critical for its phosphorylation by PKA. Moreover, PKA-Smurf1-PIPKIγ signal transduction takes a significant part in lung cancer cell growth and in vivo tumorigenesis. Thus, we propose that the PKA-Smurf1-PIPKIγ pathway has an important role in pulmonary tumorigenesis and imposes substantial clinical impact on development of novel diagnostic markers and therapeutic targets for lung cancer treatment.
The data suggest that the prevalence of PAD in a female natural population in China is higher than that in males. Many conventional risk factors and comorbidities were correlated with the high prevalence of PAD in females. But only very few female patients with PAD were diagnosed. Thus, more measures should be taken to diagnose, prevent and control PAD in females in China.
The data suggests that BaPWV, radial AI, and carotid-IMT values are positively correlated with each other, and AI values are correlated with ABI values in a U-shaped curve in a Chinese population of Inner Mongolia.
Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.
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