ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Diffuse Intrinsic Pontine Gliomas Exhibit Cell Biological and Molecular Signatures of Fetal Hindbrain-Derived Neural Progenitor Cells / 神经科学通报·英文版

Diffuse intrinsic pontine glioma (DIPG) is the main cause of brain tumor-related death among children. Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons. Here we report the human fetal hindbrain-derived neural progenitor cells (pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3K27M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.

Microsurgical management of supra- and infra-tentorial meningioma of the posterior petrous bone / 中国综合临床

Objective To explore the microsurgical experience of supra- and infra-tentorial meningioma of the posterior petrous bone.Methods Clinical data of 21 patients who had undergone microsurgical treatment were retrospectively reviewed.Results All patients underwent surgical treatment via a suboccipital retrosigmoid approach,and hyperostosis of the petrous bone and infiltrated cerebellar tentorium were resected intraoperatively.Tumor resection was categorized as Grade Ⅰ in 16 patients,Grade Ⅱ in 5 patients,according to the Simpson classification system.The main postoperative complications included slight facial paresis and hearing function deterioration.The mean follow-up time was 3.2 years.All patients resumed normal daily activity and no tumor recurrence happened.Conclusions Total resection for supra- and infra-tentorial meningioma of the posterior petrous bone can be achieved with an excellent prognosis by use of microsurgical technique.

Diagnosis, treatment and prognosis of 34 patients with malignant primary intracranial teratoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics, diagnosis and surgical treatment of malignant intracranial teratomas.</p><p><b>METHODS</b>Thirty-four patients with intracranial teratoma proved by histopathology were treated by operation. The growth pattern of this tumor, assessed by its clinical manifestations and neuroimaging together with surgical treatment and results were analyzed retrospectively.</p><p><b>RESULTS</b>Only 6 lesions had been correctly suspected as teratoma before surgery. Total removal was achieved in 14 patients with a operative mortality of 32.4%. The survival of 23 patients with lesions showing aggressive growth was significantly different from those without (P < 0.05). Nineteen of these patients did not survive beyond the sixth month after surgery.</p><p><b>CONCLUSION</b>Accurate preoperative diagnosis is difficult in malignant intracranial teratoma, especially for patients with the tumor in the sella region. The invasive biological behavior of the tumor is proved to be the main cause of surgery being dwarfed. Protection of the hypothalamus and brainstem, relief of hydrocephalus are the crucial points in surgical treatment. Comprehensive histopathologic examination combined with serum and CSF tumor marker detection is necessary for correct diagnosis and treatment.</p>