BACKGROUND: Gastric cancer (GC) shows high metastasis and low survival. RNA modification writers play critical roles in tumor development. This study examined the clinical significance of RNA modification writers in GC prognosis based on four types of adenosine modifications (m1A, m6A, APA and A-to-I). RESULTS: Writers demonstrated high mutation and expression in GC patients. Different expressions of 26 RNA modification writers were differentially associated with GC prognosis. High-WM score group appeared worse overall survival, higher immune infiltration and activation of EMT pathways than low-WM score group. WM score was correlated with both miRNAs-targeted signaling pathways and patients' sensitivity to chemotherapeutic drugs and efficacy of immunotherapy. CONCLUSIONS: This study further revealed the close association between adenosine-related RNA modifications and progression of GC. A cross talk between EMT and RNA modification was identified to be one of the mechanisms underlying GC development. Our WM scoring system could serve as a clinical indicator for predicting GC prognosis. Importantly, the WM score could guide personalized treatments such as chemotherapy and immunotherapy for GC patients.

BACKGROUND: Variants in SLC34A2 encoding the sodium-dependent phosphate transport protein 2b (NaPi-IIb) cause the rare lung disease pulmonary alveolar microlithiasis (PAM). PAM is characterised by the deposition of calcium-phosphate concretions in the alveoli usually progressing over time. No effective treatment is available. So far, 30 allelic variants in patients have been reported but only a few have been functionally characterised. This study aimed to determine the impact of selected SLC34A2 variants on transporter expression and phosphate uptake in cellular studies. METHODS: Two nonsense variants (c.910A > T and c.1456C > T), one frameshift (c.1328delT), and one in-frame deletion (c.1402_1404delACC) previously reported in patients with PAM were selected for investigation. Wild-type and mutant c-Myc-tagged human NaPi-IIb constructs were expressed in Xenopus laevis oocytes. The transport function was investigated with a 32Pi uptake assay. NaPi-IIb protein expression and localisation were determined with immunoblotting and immunohistochemistry, respectively. RESULTS: Oocytes injected with the wild-type human NaPi-IIb construct had significant 32Pi transport compared to water-injected oocytes. In addition, the protein had a molecular weight as expected for the glycosylated form, and it was readily detectable in the oocyte membrane. Although the protein from the Thr468del construct was synthesised and expressed in the oocyte membrane, phosphate transport was similar to non-injected control oocytes. All other mutants were non-functional and not expressed in the membrane, consistent with the expected impact of the truncations caused by premature stop codons. CONCLUSIONS: Of four analysed SLC34A2 variants, only the Thr468del showed similar protein expression as the wild-type cotransporter in the oocyte membrane. All mutant transporters were non-functional, supporting that dysfunction of NaPi-IIb underlies the pathology of PAM.

Diabetes is a chronic metabolic disorder that leads to the dysfunction of various tissues and organs, including eyes, kidneys, and cardiovascular system. According to the World Health Organization, diabetes prevalence is 8.8% globally among whom about 90% of cases are type 2 diabetes. There are not any significant clinical manifestations in the primary stages of diabetes. Therefore, screening can be an efficient way to reduce the diabetic complications. Over the recent decades, the prevalence of diabetes has increased alarmingly among the Middle East population, which has imposed exorbitant costs on the health care system in this region. Given that the genetic changes are among the important risk factors associated with predisposing people to diabetes, we examined the role of single-nucleotide polymorphisms (SNPs) in the pathogenesis of diabetes among Middle East population. In the present review, we assessed the molecular pathology of diabetes in the Middle East population that paves the way for introducing an efficient SNP-based diagnostic panel for diabetes screening among the Middle East population. Since, the Middle East has a population of 370 million people; the current review can be a reliable model for the introduction of SNP-based diagnostic panels in other populations and countries around the world.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults and has a poor prognosis. Recent developments in the field of high-throughput sequencing technology, particularly in methylated RNA immunoprecipitation sequencing (MeRIP-seq), have led to renewed interest in RNA methylation. Among the various RNA modifications, N6-methyladenosine (m6A) modifications are the most common. Emerging evidence suggests that m6A methylation can affect the complexity of cancer progression by regulating biological functions related to cancer. In this review, we will shed light on recent findings regarding the biological function of m6A methylation in OS and discuss future research directions and potential clinical applications of RNA methyltransferases in OS.