Abstract N6-methyladenosine (m6A) is one of widespread post-transcriptional mRNA modifications in eukaryotes and the m6A modification plays critical roles in various human cancers. However, the role of m6A-binding proteins in cancer metabolism remains elusive. Here, we report that YTH domain family 2 (YTHDF2) is upregulated in lung cancer tissues, promotes lung cancer cell growth and enhances the pentose phosphate pathway (PPP) flux, which is crucial for tumor growth. Mechanistically, YTHDF2 directly binds to the m6A modification site of 6-phosphogluconate dehydrogenase (6PGD) three prime untranslated region (3′-UTR) to promote 6PGD mRNA translation in lung cancer cells. Collectively, our data indicate that YTHDF2 acts as a tumor promoter to enhance tumor growth via facilitating 6PGD mRNA translation.

Matrine, an alkaloid compound isolated from the medicinal plant Sophora flavescens, inhibits many types of cancer proliferation. However, the precise mechanism of the matrine antihuman chronic myeloid leukemia remains unclear. In this study, we showed that matrine significantly inhibited the cell proliferation and induced apoptosis by regulating Warburg effect through controlling hexokinases 2 (HK2) expression in myeloid leukemia cells. Interestingly, matrine inhibited the expression of HK2 mediated by reduction in c-Myc binding to HK2 gene intron and led to downregulation of HK2, which upregulated proapoptotic protein Bad and then induced apoptosis. We further demonstrated that matrine could synergize with lonidamine, an inhibitor of HK2, for the treatment of myeloid leukemia, both in vitro and in vivo. Taken together, our findings reveal that matrine could promote human myeloid leukemia cells apoptosis via regulating Warburg effect by controlling HK2.

Kawasaki disease (KD) is a systemic vasculitis syndrome that leads to coronary artery aneurysm (CAA). While echocardiography is the most important imaging modality for coronary artery assessment, a specific diagnostic biomarker complementary for CAA has not been reported. We aimed to analyze the profiles of exosomal miRNAs extracted from the serum of KD patients and controls to identify candidate biomarkers for CAA. Serum samples from 39 healthy children, 42 CAA patients, 38 coronary artery dilatation (CAD) patients and 45 virus‐infected patients including 24 EBV patients and 21 ADV patients were randomly selected. Next generation sequencing was used to analyze serum exosomal miRNA to detect differentially expressed miRNAs. Biomarker candidates were validated by qRT‐PCR. One hundred (and) ninety‐six differentially expressed miRNAs (DEMs) were detected in CAA patients and healthy children. There were 70 DEMs and 140 DEMs in CAA patients versus CAD patients, and in CAA patients versus virus‐infected patients, respectively. We selected the three most upregulated (let‐7i‐3p, miR‐17‐3p, and miR‐210‐5p) and the three most downregulated miRNAs (miR‐6743‐5p, miR‐1246, and miR‐6834‐5p) in the DEMs, which were expressed differentially in CAA patients versus healthy children, and in CAA patients versus virus‐infected patients, not in virus‐infected patients versus healthy children, as biomarker candidates. Excluded DEMs of CAD and virus‐infected patients, let‐7i‐3p was detected by sequence data analysis as a biomarker candidate for CAA patients, and then validated by qRT‐PCR in a larger set of clinical samples. As a biomarker candidate, let‐7i‐3p provides an additional means of diagnosing CAA patients. Additionally, miRNA biomarkers complement ultrasonic imaging, allowing for greater diagnostic precision. © 2019 IUBMB Life, 2019

Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well-characterized as a marker of intestinal stem cells and certain types of tumor stem cells, where positive cells may develop into intestinal epithelial cells or intestinal adenomas. However, the roles of Lgr5 in the lung and in lung tumors remain unclear. An immunohistochemistry (IHC) analysis was performed to detect the expression of Lgr5 in the lung from a normal mouse. Histopathological sections of the lungs from Lgr5 heterozygous knockout mice (Lgr5+/−) were observed following with hematoxylin and eosin. Furthermore, tissue microarrays containing tumor cores from lung cancer patients were also analyzed by IHC. Lgr5-positive cells were present in the pulmonary alveoli and bronchi of normal mice, whereas the lungs of Lgr5+/− mice lost their normal morphological structure compared with the lungs of the normal mice. Lgr5 was expressed in lung adenocarcinoma, however, not in squamous carcinoma, and Lgr5 expression was positively associated with tumor, node, metastasis stage. Lgr5 is expressed in normal murine lung and is associated with TNM stage in patients with lung adenocarcinoma.

Background: We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced Non-Small Cell Lung Cancer (NSCLC). Method: We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of pre-operative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery. Result: The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. 18 (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. 6 (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 months versus 9.1 months, P ¼ 0.021). Conclusion: Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

We report a unique case of an 18-day-old girl with three coronary artery fistulas to the right atrium and right ventricle, respectively: three collateral arteries arising from the descending aorta and one from the right subclavian artery draining through a sac to the top of the right atrium, patent ductus arteriosus, and atrial septal defect. She presented symptoms of acute congestive heart failure. Cardiac catheterization and surgical interventions were performed to repair the defects. The patient recovered uneventfully and grew up well at 3 years of follow-up. Whole-genome sequencing (WES) in the patient, compared to her parents, showed 17 variants within 11 genes. Among these, only compound heterozygous mutation, c.T470G (p.L157R) and c.A1622G (p.D541G), in the DRC1 gene have been reportedly related to congenital heart disease and are the most likely causative in our patient.