No abstract

Bladder cancer-associated transcript 1 (BLACAT1) is a novel identified long noncoding RNA (lncRNA) in bladder cancer, and has been suggested to function as an oncogenic lncRNA in several types of human cancer. However, its involvement in the progression of small-cell lung cancer (SCLC) remained unknown. The aim of our study was to investigate the clinical value and biological function in SCLC. In our results, BLACAT1 expression was increased in SCLC tissues and cell lines compared with paired adjacent normal tissues and bronchial epithelial cell lines, respectively. In addition, BLACAT1 high-expression was obviously associated with advanced clinical stage, large tumor size, more lymph node metastasis, present distant metastasis, and poor prognosis. Furthermore, multivariate analysis indicated that high-expression of BLACAT1 acted as an independent poor prognostic factor for overall survival in SCLC cases. The loss-of-function studies suggested that of BLACAT1 suppressed SCLC cell proliferation, migration, and invasion, and induced G0/G1 phase arrest. In conclusion, BLACAT1 is associated with the malignant status and prognosis in patients with SCLC, and functions as an oncogenic lncRNA in regulating cell proliferation and motility, suggesting BLACAT1 may act as a potential target for SCLC prevention and treatment.

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro. Our research fills a gap which has existed in the study of inflammatory stress about the V-ATPase subunit ATP6V0D2 in liver macrophages. We first found that the expression of specific ATP6V0D2 in liver macrophages was upregulated with the induction of inflammatory cascade after liver IR surgery, and knockdown of ATP6V0D2 resulted in increased secretion of proinflammatory factors and chemokines, which enhanced activation of NLRP3 and aggravation of liver injury. Further studies found that the exacerbated activation of NLRP3 was related to the autophagic flux regulated by ATP6V0D2. Knocking down ATP6V0D2 impaired the formation of autophagolysosome and aggravated liver IR injury through nonspecific V-ATPase activation independent of V-ATPase-Notchl-Hesl signal axis. In general, we illustrated that the expression of ATP6V0D2 in liver macrophages was upregulated after liver IR, and by gradually promoting the formation of autophagolysosomes to increase autophagy flux to limit the activation of liver inflammation, this regulation is independent of the Notch1-Hes1 signal axis.

The glymphatic-lymphatic fluid transport system (GLFTS) consists of glymphatic pathway and cerebrospinal fluid (CSF) lymphatic outflow routes, allowing biological liquids from the brain parenchyma to access the CSF along with perivascular space and to be cleaned out of the skull through lymphatic vessels. It is known that increased local pressure due to physical compression of tissue improves lymphatic transport in peripheral organs, but little is known about the exact relationship between increased intracranial pressure (IICP) and GLFTS. In this study, we verify our hypothesis that IICP significantly impacts GLFTS, and this effect depends on severity of the IICP. Using a previously developed inflating balloon model to induce IICP and inject fluorescent tracers into the cisterna magna, we found significant impairment of the glymphatic circulation after IICP. We further found that cerebrovascular occlusion occurred, and cerebrovascular pulsation decreased after IICP. IICP also interrupted the drainage of deep cervical lymph nodes and dorsal meningeal lymphatic function, enhancing spinal lymphatic outflow to the sacral lymph nodes. Notably, these effects were associated with the severity of IICP. Thus, our findings proved that the intensity of IICP significantly impacts GLFTS. This may have translational applications for preventing and treating related neurological disorders.